Sample records for earthworm gut microbiota

The human intestine harbors a complex bacterial community called the gutmicrobiota. This microbiota is specific to each individual despite the existence of several bacterial species shared by the majority of adults. The influence of the gutmicrobiota in human health and disease has been revealed in the recent years. Particularly, the use of germ-free animals and microbiota transplant showed that the gutmicrobiota may play a causal role in the development of obesity and associated metabolic disorders, and lead to identification of several mechanisms. In humans, differences in microbiota composition, functional genes and metabolic activities are observed between obese and lean individuals suggesting a contribution of the gutmicrobiota to these phenotypes. Finally, the evidence linking gut bacteria to host metabolism could allow the development of new therapeutic strategies based on gutmicrobiota modulation to treat or prevent obesity.

Gutmicrobiota regulates intestinal and extraintestinal homeostasis. Accumulating evidence suggests that the gutmicrobiota may also regulate brain function and behavior. Results from animal models indicate that disturbances in the composition and functionality of some microbiota members are associated with neurophysiological disorders, strengthening the idea of a microbiota-gut-brain axis and the role of microbiota as a peacekeeper in the brain health. Here, we review recent discoveries on t...

The in vivo production of nitrous oxide (N2O) by earthworms is due to their gutmicrobiota, and it is hypothesized that the microenvironment of the gut activates ingested N2O-producing soil bacteria. In situ measurement of N2O and O2 with microsensors demonstrated that the earthwormgut is anoxic and the site of N2O production. The gut had a pH of 6.9 and an average water content of approximately 50%. The water content within the gut decreased from the anterior end to the posterior end. In co...

Objective:To systematically review the updated information about the gutmicrobiota-brain axis.Data Sources:All articles about gutmicrobiota-brain axis published up to July 18,2016,were identified through a literature search on PubMed,ScienceDirect,and Web of Science,with the keywords of"gutmicrobiota","gut-brain axis",and "neuroscience".Study Selection:All relevant articles on gutmicrobiota and gut-brain axis were included and carefully reviewed,with no limitation of study design.Results:It is well-recognized that gutmicrobiota affects the brain's physiological,behavioral,and cognitive functions although its precise mechanism has not yet been fully understood.Gutmicrobiota-brain axis may include gutmicrobiota and their metabolic products,enteric nervous system,sympathetic and parasympathetic branches within the autonomic nervous system,neural-immune system,neuroendocrine system,and central nervous system.Moreover,there may be five communication routes between gutmicrobiota and brain,including the gut-brain's neural network,neuroendocrine-hypothalamic-pituitary-adrenal axis,gut immune system,some neurotransmitters and neural regulators synthesized by gut bacteria,and barrier paths including intestinal mucosal barrier and blood-brain barrier.The microbiome is used to define the composition and functional characteristics of gutmicrobiota,and metagenomics is an appropriate technique to characterize gutmicrobiota.Conclusions:Gutmicrobiota-brain axis refers to a bidirectional information network between the gutmicrobiota and the brain,which may provide a new way to protect the brain in the near future.

The microbiota in our gut performs many different essential functions that help us to stay healthy. These functions include vitamin production, regulation of lipid metabolism and short chain fatty acid production as fuel for epithelial cells and regulation of gene expression. There is a very numerou

The microbiota in our gut performs many different essential functions that help us to stay healthy. These functions include vitamin production, regulation of lipid metabolism and short chain fatty acid production as fuel for epithelial cells and regulation of gene expression. There is a very

Objective: To systematically review the updated information about the gutmicrobiota-brain axis. Data Sources: All articles about gutmicrobiota-brain axis published up to July 18, 2016, were identified through a literature search on PubMed, ScienceDirect, and Web of Science, with the keywords of “gut microbiota”, “gut-brain axis”, and “neuroscience”. Study Selection: All relevant articles on gutmicrobiota and gut-brain axis were included and carefully reviewed, with no limitation of study design. Results: It is well-recognized that gutmicrobiota affects the brain's physiological, behavioral, and cognitive functions although its precise mechanism has not yet been fully understood. Gutmicrobiota-brain axis may include gutmicrobiota and their metabolic products, enteric nervous system, sympathetic and parasympathetic branches within the autonomic nervous system, neural-immune system, neuroendocrine system, and central nervous system. Moreover, there may be five communication routes between gutmicrobiota and brain, including the gut-brain's neural network, neuroendocrine-hypothalamic-pituitary-adrenal axis, gut immune system, some neurotransmitters and neural regulators synthesized by gut bacteria, and barrier paths including intestinal mucosal barrier and blood-brain barrier. The microbiome is used to define the composition and functional characteristics of gutmicrobiota, and metagenomics is an appropriate technique to characterize gutmicrobiota. Conclusions: Gutmicrobiota-brain axis refers to a bidirectional information network between the gutmicrobiota and the brain, which may provide a new way to protect the brain in the near future. PMID:27647198

Full Text Available Gutmicrobiota plays critical physiological roles in the energy extraction and in the control of local or systemic immunity. Gutmicrobiota and its disturbance also appear to be involved in the pathogenesis of diverse diseases including metabolic disorders, gastrointestinal diseases, cancer, etc. In the metabolic point of view, gutmicrobiota can modulate lipid accumulation, lipopolysaccharide content and the production of short-chain fatty acids that affect food intake, inflammatory tone, or insulin signaling. Several strategies have been developed to change gutmicrobiota such as prebiotics, probiotics, certain antidiabetic drugs or fecal microbiota transplantation, which have diverse effects on body metabolism and on the development of metabolic disorders.

Objective: To systematically review the updated information about the gutmicrobiota-brain axis. Data Sources: All articles about gutmicrobiota-brain axis published up to July 18, 2016, were identified through a literature search on PubMed, ScienceDirect, and Web of Science, with the keywords of “gut microbiota”, “gut-brain axis”, and “neuroscience”. Study Selection: All relevant articles on gutmicrobiota and gut-brain axis were included and carefully reviewed, with no limitation of s...

Full Text Available Gutmicrobiota regulates intestinal and extraintestinal homeostasis. Accumulating evidence suggests that the gutmicrobiota may also regulate brain function and behavior. Results from animal models indicate that disturbances in the composition and functionality of some microbiota members are associated with neurophysiological disorders, strengthening the idea of a microbiota-gut-brain axis and the role of microbiota as a peacekeeper in the brain health. Here, we review recent discoveries on the role of the gutmicrobiota in central nervous system (CNS-related diseases. We also discuss the emerging concept of the bidirectional regulation by the circadian rhythm and gutmicrobiota, and the potential role of the epigenetic regulation in neuronal cell function. Microbiome studies are also highlighted as crucial in the development of targeted therapies for neurodevelopmental disorders.

Gutmicrobiota plays critical physiological roles in the energy extraction and in the control of local or systemic immunity. Gutmicrobiota and its disturbance also appear to be involved in the pathogenesis of diverse diseases including metabolic disorders, gastrointestinal diseases, cancer, etc. In the metabolic point of view, gutmicrobiota can modulate lipid accumulation, lipopolysaccharide content and the production of short-chain fatty acids that affect food intake, inflammatory tone, or...

Gutmicrobiota regulates intestinal and extraintestinal homeostasis. Accumulating evidence suggests that the gutmicrobiota may also regulate brain function and behavior. Results from animal models indicate that disturbances in the composition and functionality of some microbiota members are associated with neurophysiological disorders, strengthening the idea of a microbiota–gut–brain axis and the role of microbiota as a “peacekeeper” in the brain health. Here, we review recent discoveries on the role of the gutmicrobiota in central nervous system-related diseases. We also discuss the emerging concept of the bidirectional regulation by the circadian rhythm and gutmicrobiota, and the potential role of the epigenetic regulation in neuronal cell function. Microbiome studies are also highlighted as crucial in the development of targeted therapies for neurodevelopmental disorders. PMID:27014255

The accruing data linking the gutmicrobiota to the development and function of the central nervous system has been proposed as a paradigm shift in neuroscience. Neuroimmune, neuroendocrine and neural communication pathways exist between host and microbe. These pathways are components of the brain-gut-microbiota axis and preclinical evidence suggests that the microbiota can recruit this bidirectional communication system to modulate brain development, function and behaviour. Dysfunctional neu...

Several studies revealed that gutmicrobiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gutmicrobiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gutmicrobiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gutmicrobiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases.

Gutmicrobiota of higher vertebrates is host-specific. The number and diversity of the organisms residing within the gut ecosystem are defined by physiological and environmental factors, such as host genotype, habitat, and diet. Recently, culture-independent sequencing techniques have added a new dimension to the study of gutmicrobiota and the challenge to analyze the large volume of sequencing data is increasingly addressed by the development of novel computational tools and methods. Interestingly, gutmicrobiota maintains a constant relative abundance at operational tax-onomic unit (OTU) levels and altered bacterial abundance has been associated with complex diseases such as symptomatic atherosclerosis, type 2 diabetes, obesity, and colorectal cancer. Therefore, the study of gut microbial population has emerged as an important field of research in order to ulti-mately achieve better health. In addition, there is a spontaneous, non-linear, and dynamic interac-tion among different bacterial species residing in the gut. Thus, predicting the influence of perturbed microbe–microbe interaction network on health can aid in developing novel therapeutics. Here, we summarize the population abundance of gutmicrobiota and its variation in different clinical states, computational tools available to analyze the pyrosequencing data, and gut microbe–microbe inter-action networks.

Full Text Available Gutmicrobiota of higher vertebrates is host-specific. The number and diversity of the organisms residing within the gut ecosystem are defined by physiological and environmental factors, such as host genotype, habitat, and diet. Recently, culture-independent sequencing techniques have added a new dimension to the study of gutmicrobiota and the challenge to analyze the large volume of sequencing data is increasingly addressed by the development of novel computational tools and methods. Interestingly, gutmicrobiota maintains a constant relative abundance at operational taxonomic unit (OTU levels and altered bacterial abundance has been associated with complex diseases such as symptomatic atherosclerosis, type 2 diabetes, obesity, and colorectal cancer. Therefore, the study of gut microbial population has emerged as an important field of research in order to ultimately achieve better health. In addition, there is a spontaneous, non-linear, and dynamic interaction among different bacterial species residing in the gut. Thus, predicting the influence of perturbed microbe–microbe interaction network on health can aid in developing novel therapeutics. Here, we summarize the population abundance of gutmicrobiota and its variation in different clinical states, computational tools available to analyze the pyrosequencing data, and gut microbe–microbe interaction networks.

The latest high-throughput sequencing technologies show that there are more than 1000 types of microbiota in the human gut. These microbes are not only important to maintain human health, but also closely related to the occurrence and development of various diseases. With the development of transplantation technologies, allogeneic transplantation has become an effective therapy for a variety of end-stage diseases. However, complications after transplantation still restrict its further development. Post-transplantation complications are closely associated with a host's immune system. There is also an interaction between a person's gutmicrobiota and immune system. Recently, animal and human studies have shown that gut microbial populations and diversity are altered after allogeneic transplantations, such as liver transplantation (LT), small bowel transplantation (SBT), kidney transplantation (KT) and hematopoietic stem cell transplantation (HTCT). Moreover, when complications, such as infection, rejection and graft versus host disease (GVHD) occur, gut microbial populations and diversity present a significant dysbiosis. Several animal and clinical studies have demonstrated that taking probiotics and prebiotics can effectively regulate gutmicrobiota and reduce the incidence of complications after transplantation. However, the role of intestinal decontamination in allogeneic transplantation is controversial. This paper reviews gut microbial status after transplantation and its relationship with complications. The role of intervention methods, including antibiotics, probiotics and prebiotics, in complications after transplantation are also discussed. Further research in this new field needs to determine the definite relationship between gut microbial dysbiosis and complications after transplantation. Additionally, further research examining gut microbial intervention methods to ameliorate complications after transplantation is warranted. A better understanding of the

Recent evidence regarding celiac disease has increasingly shown the role of innate immunity in triggering the immune response by stimulating the adaptive immune response and by mucosal damage. The interaction between the gutmicrobiota and the mucosal wall is mediated by the same receptors which can activate innate immunity. Thus, changes in gutmicrobiota may lead to activation of this inflammatory pathway. This paper is a review of the current knowledge regarding the relationship between celiac disease and gutmicrobiota. In fact, patients with celiac disease have a reduction in beneficial species and an increase in those potentially pathogenic as compared to healthy subjects. This dysbiosis is reduced, but might still remain, after a gluten-free diet. Thus, gutmicrobiota could play a significant role in the pathogenesis of celiac disease, as described by studies which link dysbiosis with the inflammatory milieu in celiac patients. The use of probiotics seems to reduce the inflammatory response and restore a normal proportion of beneficial bacteria in the gastrointestinal tract. Additional evidence is needed in order to better understand the role of gutmicrobiota in the pathogenesis of celiac disease, and the clinical impact and therapeutic use of probiotics in this setting.

The exploration of the gutmicrobiota has intensified within the past decade with the introduction of cultivation-independent methods. By investigation of the gut bacterial genes, our understanding of the compositional and functional capability of the gut microbiome has increased. It is now widel...... strategies to prevent or treat type 2 diabetes....... recognized that the gutmicrobiota has profound effect on host metabolism and recently changes in the gutmicrobiota have been associated with type 2 diabetes. Animal models and human studies have linked changes in the gutmicrobiota to the induction of low-grade inflammation, altered immune response...

Full Text Available This review introduces and discusses data regarding fundamental and applied investigations in mammalian epigenomics and gutmicrobiota received over the last 10 years. Analysis of these data enabled the author first to come to the conclusion that the multiple low molecular weight substances of indigenous gutmicrobiota origin should be considered one of the main endogenous factors actively participating in epigenomic mechanisms that responsible for the mammalian genome reprogramming and post-translated modifications. Gut microecological imbalance coursed by various biogenic and abiogenic agents and factors can produce the different epigenetic abnormalities and the onset and progression of metabolic diseases associated. The author substantiates the necessity to create an international project ‘Human GutMicrobiota and Epigenomics’ that facilitates interdisciplinary collaborations among scientists and clinicians engaged in host microbial ecology, nutrition, metagenomics, epigenomics and metabolomics investigations as well as in diseases prevention and treatment. Some priority scientific and applied directions in the current omic technologies coupled with gnotobiological approaches are suggested that can open a new era in characterizing the role of the symbiotic microbiota small metabolic and signal molecules in the host epigenomics. Although discussed subject is only at an early stage its validation can open novel approaches in drug discovery studies.

Gutmicrobiota exerts a significant role in the pathogenesis of the metabolic syndrome, as confirmed by studies conducted both on humans and animal models. Gut microbial composition and functions are strongly influenced by diet. This complex intestinal "superorganism" seems to affect host metabolic balance modulating energy absorption, gut motility, appetite, glucose and lipid metabolism, as well as hepatic fatty storage. An impairment of the fine balance between gut microbes and host's immune system could culminate in the intestinal translocation of bacterial fragments and the development of "metabolic endotoxemia", leading to systemic inflammation and insulin resistance. Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition, that seem to affect the success, or the inefficacy, of treatment strategies. Manipulation of gutmicrobiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity, thus, ameliorating metabolic balance and promoting weight loss. However, further evidence is needed to better understand their clinical impact and therapeutic use.

The human gut is densely populated by commensal and symbiotic microbes (the "gutmicrobiota"), with the majority of the constituent microorganisms being bacteria. Accumulating evidence indicates that the gutmicrobiota plays a significant role in the development of obesity, obesity-associated inflam...

The human gutmicrobiota plays an important role for the health of the host. The question is whether we can modulate the gutmicrobiota by changing diet. During a 6-month, randomised, controlled dietary intervention, the effect of a moderate diet shift from Average Danish Diet to New Nordic Diet...... on the gutmicrobiota in humans (n=62) was investigated. Quantitative PCR analysis showed that the microbiota did not change significantly by the intervention. Nevertheless, by stratifying subjects into two enterotypes, distinguished by the Prevotella/Bacteroides ratio (P/B), we were able to detect...... significant changes in the gutmicrobiota composition resulting from the interventions. Subjects with a high-P/B experienced more pronounced changes in the gutmicrobiota composition than subjects with a low-P/B. The study is the first to indicate that enterotypes influence microbiota response to a dietary...

Gutmicrobiota is known to have a relevant role in our health, and is also related to both gastrointestinal and extradigestive diseases. Therefore, restoring the alteration of gutmicrobiota represents an outstanding clinical target for the treatment of gutmicrobiota-related diseases. The modulation of gutmicrobiota is perhaps an ancestral, innate concept for human beings. At this time, the restoration of gutmicrobiota impairment is a well-established concept in mainstream medicine, and several therapeutic approaches have been developed in this regard. Antibiotics, prebiotics and probiotics are the best known and commercially available options to overcome gastrointestinal dysbiosis. Fecal microbiota transplantation is an old procedure that has recently become popular again. It has shown a clear effectiveness in the treatment of C. difficile infection, and now represents a cutting-edge option for the restoration of gutmicrobiota. Nevertheless, such weapons should be used with caution. Antibiotics can indeed harm and alter gutmicrobiota composition. Probiotics, instead, are not at all the same thing, and thinking in terms of different strains is probably the only way to improve clinical outcomes. Moreover, fecal microbiota transplantation has shown promising results, but stronger proofs are needed. Considerable efforts are needed to increase our knowledge in the field of gutmicrobiota, especially with regard to the future use in its modulation for therapeutic purposes.

The human gutmicrobiota plays an important role for human health. The question is whether we can modulate the gutmicrobiota by changing diet. During a 6-month, randomised, controlled dietary intervention, the effect of consuming a diet following the New Nordic Diet recommendations (NND......) as opposed to Average Danish Diet (ADD) on the gutmicrobiota in humans (n=62) was investigated. Quantitative PCR analysis showed that the microbiota did not change significantly by the intervention. Nevertheless, by stratifying subjects into two enterotypes, distinguished by the Prevotella/Bacteroides ratio...... (P/B), we were able to detect significant changes in the gutmicrobiota composition resulting from the interventions. Subjects with a high-P/B experienced more pronounced changes in the gutmicrobiota composition than subjects with a low-P/B. The study is the first to indicate that enterotypes...

Full Text Available Systemic and local inflammation in relation to the resident microbiota of the human gastro-intestinal (GI tract and administration of probiotics are the main themes of the present review. The dominating taxa of the human GI tract and their potential for aggravating or suppressing inflammation are described. The review focuses on human trials with probiotics and does not include in vitro studies and animal experimental models. The applications of probiotics considered are systemic immune-modulation, the metabolic syndrome, liver injury, inflammatory bowel disease, colorectal cancer and radiation-induced enteritis. When the major genomic differences between different types of probiotics are taken into account, it is to be expected that the human body can respond differently to the different species and strains of probiotics. This fact is often neglected in discussions of the outcome of clinical trials with probiotics.

There is a strong relationship between liver and gut; while the portal venous system receives blood from the gut, and its contents may affect liver functions, liver in turn, affects intestinal functions through bile secretion. There is robust evidence that the pathogenesis of hepatic encephalopathy (HE) is linked to alterations in gutmicrobiota and their by-products such as ammonia, indoles, oxindoles, endotoxins, etc. In the setting of intestinal barrier and immune dysfunction, these by-products are involved in the pathogenesis of complications of liver cirrhosis including HE and systemic inflammation plays an important role. Prebiotics, probiotics and synbiotics may exhibit efficacy in the treatment of HE by modulating the gut flora. They improve derangement in flora by decreasing the counts of pathogenic bacteria and thus improving the endotoxemia, HE and the liver disease. Current evidence suggest that the trials evaluating the role of probiotics in the treatment of HE are of not high quality and all trials had high risk of bias and high risk of random errors. Therefore, the use of probiotics for patients with HE cannot be currently recommended. Further RCTs are required. This review summarizes the main literature findings about the relationships between gut flora and HE, both in terms of the pathogenesis and the treatment of HE.

The last decade has witnessed a growing appreciation of the fundamental role played by an early assembly of a diverse and balanced gutmicrobiota and its subsequent maintenance for future health of the host. Gutmicrobiota is currently viewed as a key regulator of a fluent bidirectional dialogue between the gut and the brain (gut-brain axis). A number of preclinical studies have suggested that the microbiota and its genome (microbiome) may play a key role in neurodevelopmental and neurodegenerative disorders. Furthermore, alterations in the gutmicrobiota composition in humans have also been linked to a variety of neuropsychiatric conditions, including depression, autism and Parkinson’s disease. However, it is not yet clear whether these changes in the microbiome are causally related to such diseases or are secondary effects thereof. In this respect, recent studies in animals have indicated that gutmicrobiota transplantation can transfer a behavioral phenotype, suggesting that the gutmicrobiota may be a modifiable factor modulating the development or pathogenesis of neuropsychiatric conditions. Further studies are warranted to establish whether or not the findings of preclinical animal experiments can be generalized to humans. Moreover, although different communication routes between the microbiota and brain have been identified, further studies must elucidate all the underlying mechanisms involved. Such research is expected to contribute to the design of strategies to modulate the gutmicrobiota and its functions with a view to improving mental health, and thus provide opportunities to improve the management of psychiatric diseases. Here, we review the evidence supporting a role of the gutmicrobiota in neuropsychiatric disorders and the state of the art regarding the mechanisms underlying its contribution to mental illness and health. We also consider the stages of life where the gutmicrobiota is more susceptible to the effects of environmental stressors

The gut immune system has a key role in the development of autoimmune diabetes, and factors that control the gut immune system are also regulators of beta-cell autoimmunity. Gutmicrobiota modulate the function of the gut immune system by their effect on the innate immune system, such as the intestinal epithelial cells and dendritic cells, and on the adaptive immune system, in particular intestinal T cells. Due to the immunological link between gut and pancreas, e.g. the shared lymphocyte homing receptors, the immunological changes in the gut are reflected in the pancreas. According to animal studies, changes in gutmicrobiota alter the development of autoimmune diabetes. This has been demonstrated by antibiotics that induce changes in the gutmicrobiota. Furthermore, gut-colonizing microbes may modify the incidence of autoimmune diabetes in animal models. Deficient toll-like receptor (TLR) signaling, mediating microbial stimulus in immune cells, prevents autoimmune diabetes, which appears to be dependent on alterations in the intestinal microbiota. Although few studies have been conducted in humans, recent studies suggest that the abundance of Bacteroides and lack of butyrate-producing bacteria in fecal microbiota are associated with beta-cell autoimmunity and type 1 diabetes. It is possible that altered gutmicrobiota are associated with immunological aberrancies in type 1 diabetes. The changes in gutmicrobiota could lead to alterations in the gut immune system, such as increased gut permeability, small intestinal inflammation, and impaired tolerance to food antigens, all of which are observed in type 1 diabetes. Poor fitness of gutmicrobiota could explain why children who develop type 1 diabetes are prone to enterovirus infections, and do not develop tolerance to cow milk antigens. These candidate risk factors of type 1 diabetes may imply an increased risk of type 1 diabetes due to the presence of gutmicrobiota that do not support health. Despite the complex

Relation between the gutmicrobiota and human health is being increasingly recognised. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal human gutmicrobiota comprises of two major phyla, namely Bacteroidetes and Firmicutes. Though the gutmicrobiota in an infant appears haphazard, it starts resembling the adult flora by the age of 3 years. Nevertheless, there exist temporal and spatial variations in the microbial distribution from esophagus to the rectum all along the individual's life span. Developments in genome sequencing technologies and bioinformatics have now enabled scientists to study these microorganisms and their function and microbe-host interactions in an elaborate manner both in health and disease. The normal gutmicrobiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Several factors play a role in shaping the normal gutmicrobiota. They include (1) the mode of delivery (vaginal or caesarean); (2) diet during infancy (breast milk or formula feeds) and adulthood (vegan based or meat based); and (3) use of antibiotics or antibiotic like molecules that are derived from the environment or the gut commensal community. A major concern of antibiotic use is the long-term alteration of the normal healthy gutmicrobiota and horizontal transfer of resistance genes that could result in reservoir of organisms with a multidrug resistant gene pool.

The human gutmicrobiota has been studied for more than a century. However, of nonculture-based techniques exploiting next-generation sequencing for analysing the microbiota, development has renewed research within the field during the past decade. The observation that the gutmicrobiota......, as an environmental factor, contributes to adiposity has further increased interest in the field. The human microbiota is affected by the diet, and macronutrients serve as substrates for many microbially produced metabolites, such as short-chain fatty acids and bile acids, that may modulate host metabolism. Obesity......-producing bacteria might be causally linked to type 2 diabetes. Bariatric surgery, which promotes long-term weight loss and diabetes remission, alters the gutmicrobiota in both mice and humans. Furthermore, by transferring the microbiota from postbariatric surgery patients to mice, it has been demonstrated...

Childhood malnutrition is a global health problem that cannot be attributed to food insecurity alone. The gutmicrobiota may contribute to this devastating health disorder. In this Perspective, we call for the application of tools and concepts emerging from studies of the human gutmicrobiota to better understand the nutritional needs of infants and children and the role of the microbiota in the pathogenesis and treatment of undernutrition. This effort will require elucidation of the interrelationships between breast milk composition and the development of the microbiota and immune system in the context of the maternal-infant dyad.

Full Text Available BACKGROUND: Earthworms are an ecosystem's engineers, contributing to a wide range of nutrient cycling and geochemical processes in the ecosystem. Their activities can increase rates of silicate mineral weathering. Their intestinal microbes usually are thought to be one of the key drivers of mineral degradation mediated by earthworms,but the diversities of the intestinal microorganisms which were relevant with mineral weathering are unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we show earthworms' effect on silicate mineral weathering and the responses of bacterial communities in their gut and surrounding substrates after being fed with potassium-bearing rock powder (PBRP. Determination of water-soluble and HNO(3-extractable elements indicated some elements such as Al, Fe and Ca were significantly released from mineral upon the digestion of earthworms. The microbial communities in earthworms' gut and the surrounding substrates were investigated by amplified ribosomal DNA restriction analysis (ARDRA and the results showed a higher bacterial diversity in the guts of the earthworms fed with PBRP and the PBRP after being fed to earthworms. UPGMA dendrogram with unweighted UniFrac analysis, considering only taxa that are present, revealed that earthworms' gut and their surrounding substrate shared similar microbiota. UPGMA dendrogram with weighted UniFrac, considering the relative abundance of microbial lineages, showed the two samples from surrounding substrate and the two samples from earthworms' gut had similarity in microbial community, respectively. CONCLUSIONS/SIGNIFICANCE: Our results indicated earthworms can accelerate degradation of silicate mineral. Earthworms play an important role in ecosystem processe since they not only have some positive effects on soil structure, but also promote nutrient cycling of ecosystem by enhancing the weathering of minerals.

Advances in tools for molecular investigations have allowed deeper understanding of how microbes can influence host physiology. A very interesting field of research that has gained attention recently is the possible role of gutmicrobiota in the development of obesity and metabolic disorders. The aim of this review is to discuss mechanisms that explain the influence of gutmicrobiota on host metabolism. The gutmicrobiota is important for normal physiology of the host. However, differences in their composition may have different impacts on host metabolism. It has been shown that obese and lean subjects present different microbiota composition profile. These differences in microbiota composition may contribute to weight imbalance and impaired metabolism. The evidences from animal models suggest that it is possible that the microbiota of obese subjects has higher capacity to harvest energy from the diet providing substrates that can activate lipogenic pathways. In addition, microorganisms can also influence the activity of lipoprotein lipase interfering in the accumulation of triglycerides in the adipose tissue. The interaction of gutmicrobiota with the endocannabinoid system provides a route through which intestinal permeability can be altered. Increased intestinal permeability allows the entrance of endotoxins to the circulation, which are related to the induction of inflammation and insulin resistance in mice. The impact of the proposed mechanisms for humans still needs further investigations. However, the fact that gutmicrobiota can be modulated through dietary components highlights the importance to study how fatty acids, carbohydrates, micronutrients, prebiotics, and probiotics can influence gutmicrobiota composition and the management of obesity. Gutmicrobiota seems to be an important and promising target in the prevention and treatment of obesity and its related metabolic disturbances in future studies and in clinical practice.

The hypothesis of an important role of gutmicrobiota in the maintenance of physiological state into the gastrointestinal (GI) system is supported by several studies that have shown a qualitative and quantitative alteration of the intestinal flora in a number of gastrointestinal and extra-gastrointestinal diseases. In the last few years, the importance of gutmicrobiota impairment in the etiopathogenesis of pathology such as autism, dementia and mood disorder, has been raised. The evidence of the inflammatory state alteration, highlighted in disorders such as schizophrenia, major depressive disorder and bipolar disorder, strongly recalls the microbiota alteration, highly suggesting an important role of the alteration of GI system also in neuropsychiatric disorders. Up to now, available evidences display that the impairment of gutmicrobiota plays a key role in the development of autism and mood disorders. The application of therapeutic modulators of gutmicrobiota to autism and mood disorders has been experienced only in experimental settings to date, with few but promising results. A deeper assessment of the role of gutmicrobiota in the development of autism spectrum disorder (ASD), as well as the advancement of the therapeutic armamentarium for the modulation of gutmicrobiota is warranted for a better management of ASD and mood disorders.

Diabetes is a condition of multifactorial origin, involving several molecular mechanisms related to the intestinal microbiota for its development. In type 2 diabetes, receptor activation and recognition by microorganisms from the intestinal lumen may trigger inflammatory responses, inducing the phosphorylation of serine residues in insulin receptor substrate-1, reducing insulin sensitivity. In type 1 diabetes, the lowered expression of adhesion proteins within the intestinal epithelium favours a greater immune response that may result in destruction of pancreatic β cells by CD8+ T-lymphocytes, and increased expression of interleukin-17, related to autoimmunity. Research in animal models and humans has hypothesized whether the administration of probiotics may improve the prognosis of diabetes through modulation of gutmicrobiota. We have shown in this review that a large body of evidence suggests probiotics reduce the inflammatory response and oxidative stress, as well as increase the expression of adhesion proteins within the intestinal epithelium, reducing intestinal permeability. Such effects increase insulin sensitivity and reduce autoimmune response. However, further investigations are required to clarify whether the administration of probiotics can be efficiently used for the prevention and management of diabetes.

Conclusion: The present review provides a comprehensive overview of how gutmicrobiota may have a key role in controlling the oxidative stress and inflammatory responses as well as improving metabolism and energy expenditure during intense exercise.

Hypertension is the leading risk factor for heart disease and stroke, and is estimated to cause 9.4 million deaths globally every year. The pathogenesis of hypertension is complex, but lifestyle factors such as diet are important contributors to the disease. High dietary intake of fruit and vegetables is associated with reduced blood pressure and lower cardiovascular mortality. A critical relationship between dietary intake and the composition of the gutmicrobiota has been described in the literature, and a growing body of evidence supports the role of the gutmicrobiota in the regulation of blood pressure. In this Review, we describe the mechanisms by which the gutmicrobiota and its metabolites, including short-chain fatty acids, trimethylamine N-oxide, and lipopolysaccharides, act on downstream cellular targets to prevent or contribute to the pathogenesis of hypertension. These effects have a direct influence on tissues such as the kidney, the endothelium, and the heart. Finally, we consider the role of the gutmicrobiota in resistant hypertension, the possible intergenerational effect of the gutmicrobiota on blood pressure regulation, and the promising therapeutic potential of gutmicrobiota modification to improve health and prevent disease.

The human gut is densely populated by commensal and symbiotic microbes (the "gutmicrobiota"), with the majority of the constituent microorganisms being bacteria. Accumulating evidence indicates that the gutmicrobiota plays a significant role in the development of obesity, obesity-associated inflammation and insulin resistance. In this review we discuss molecular and cell biological mechanisms by which the microbiota participate in host functions that impact the development and maintenance of the obese state, including host ingestive behavior, energy harvest, energy expenditure and fat storage. We additionally explore the diverse signaling pathways that regulate gut permeability and bacterial translocation to the host and how these are altered in the obese state to promote the systemic inflammation ("metabolic endotoxemia") that is a hallmark of obesity and its complications. Fundamental to our discussions is the concept of "crosstalk", i.e., the biochemical exchange between host and microbiota that maintains the metabolic health of the superorganism and whose dysregulation is a hallmark of the obese state. Differences in community composition, functional genes and metabolic activities of the gutmicrobiota appear to distinguish lean vs obese individuals, suggesting that gut 'dysbiosis' contributes to the development of obesity and/or its complications. The current challenge is to determine the relative importance of obesity-associated compositional and functional changes in the microbiota and to identify the relevant taxa and functional gene modules that promote leanness and metabolic health. As diet appears to play a predominant role in shaping the microbiota and promoting obesity-associated dysbiosis, parallel initiatives are required to elucidate dietary patterns and diet components (e.g., prebiotics, probiotics) that promote healthy gutmicrobiota. How the microbiota promotes human health and disease is a rich area of investigation that is likely to generate

Full Text Available The human microbiota is an aggregate of microorganisms residing in the human body, mostly in the gastrointestinal tract (GIT. Our gutmicrobiota evolves with us and plays a pivotal role in human health and disease. In recent years, the microbiota has gained increasing attention due to its impact on host metabolism, physiology, and immune system development, but also because the perturbation of the microbiota may result in a number of diseases. The gutmicrobiota may be linked to malignancies such as gastric cancer and colorectal cancer. It may also be linked to disorders such as nonalcoholic fatty liver disease (NAFLD; obesity and diabetes, which are characterized as “lifestyle diseases” of the industrialized world; coronary heart disease; and neurological disorders. Although the revolution in molecular technologies has provided us with the necessary tools to study the gutmicrobiota more accurately, we need to elucidate the relationships between the gutmicrobiota and several human pathologies more precisely, as understanding the impact that the microbiota plays in various diseases is fundamental for the development of novel therapeutic strategies. Therefore, the aim of this review is to provide the reader with an updated overview of the importance of the gutmicrobiota for human health and the potential to manipulate gut microbial composition for purposes such as the treatment of antibiotic-resistant Clostridium difficile (C. difficile infections. The concept of altering the gut community by microbial intervention in an effort to improve health is currently in its infancy. However, the therapeutic implications appear to be very great. Thus, the removal of harmful organisms and the enrichment of beneficial microbes may protect our health, and such efforts will pave the way for the development of more rational treatment options in the future.

Full Text Available Gutmicrobiota is the community of live microorganisms residing in the digestive tract. There are many groups of researchers worldwide that are working at deciphering the collective genome of the human microbiota. Modern techniques for studying the microbiota have made us aware of an important number of nonculturable bacteria and of the relation between the microorganisms that live inside us and our homeostasis. The microbiota is essential for correct body growth, the development of immunity, and nutrition. Certain epidemics affecting humanity such as asthma and obesity may possibly be explained, at least partially, by alterations in the microbiota. Dysbiosis has been associated with a series of gastrointestinal disorders that include non-alcoholic fatty liver disease, celiac disease, and irritable bowel syndrome. The present article deals with the nomenclature, modern study techniques, and functions of gutmicrobiota, and its relation to health and disease.

The human body is colonized by a vast number of microorganisms collectively defined as the microbiota. In the gut, the microbiota has important roles in health and disease, and can serve as a host of antibiotic resistance genes. Disturbances in the ecological balance, e.g. by antibiotics, can affect

The human body is colonized by a vast number of microorganisms collectively defined as the microbiota. In the gut, the microbiota has important roles in health and disease, and can serve as a host of antibiotic resistance genes. Disturbances in the ecological balance, e.g. by antibiotics, can affect

The human gutmicrobiota directly affects human health, and its alteration can lead to gastrointestinal abnormalities and inflammation. Rett syndrome (RTT), a progressive neurological disorder mainly caused by mutations in MeCP2 gene, is commonly associated with gastrointestinal dysfunctions and constipation, suggesting a link between RTT's gastrointestinal abnormalities and the gutmicrobiota. The aim of this study was to evaluate the bacterial and fungal gutmicrobiota in a cohort of RTT subjects integrating clinical, metabolomics and metagenomics data to understand if changes in the gutmicrobiota of RTT subjects could be associated with gastrointestinal abnormalities and inflammatory status. Our findings revealed the occurrence of an intestinal sub-inflammatory status in RTT subjects as measured by the elevated values of faecal calprotectin and erythrocyte sedimentation rate. We showed that, overall, RTT subjects harbour bacterial and fungal microbiota altered in terms of relative abundances from those of healthy controls, with a reduced microbial richness and dominated by microbial taxa belonging to Bifidobacterium, several Clostridia (among which Anaerostipes, Clostridium XIVa, Clostridium XIVb) as well as Erysipelotrichaceae, Actinomyces, Lactobacillus, Enterococcus, Eggerthella, Escherichia/Shigella and the fungal genus Candida. We further observed that alterations of the gutmicrobiota do not depend on the constipation status of RTT subjects and that this dysbiotic microbiota produced altered short chain fatty acids profiles. We demonstrated for the first time that RTT is associated with a dysbiosis of both the bacterial and fungal component of the gutmicrobiota, suggesting that impairments of MeCP2 functioning favour the establishment of a microbial community adapted to the costive gastrointestinal niche of RTT subjects. The altered production of short chain fatty acids associated with this microbiota might reinforce the constipation status of RTT

Modulation of the gutmicrobiota is an area of growing interest, particularly for its link to improving and maintaining the systemic health of the host. It has been suggested to have potential to reduce risk factors associated with chronic diseases, such as elevated cholesterol levels in coronary heart disease (CHD). Diets of our evolutionary ancestors were largely based on plant foods, high in dietary fiber and fermentable substrate, and our gutmicrobiota has evolved against a background of such diets. Therapeutic diets that mimic plant-based diets from the early phases of human evolution may result in drug-like cholesterol reductions. In contrast, typical Western diets low in dietary fiber and fermentable substrate, and high in saturated and trans fatty acids, are likely contributors to the increased need for pharmacological agents for cholesterol reduction. The gutmicrobiota of those consuming a Western diet are likely underutilized and depleted of metabolic fuels, resulting in a less than optimal gut microbial profile. As a result, this diet is mismatched to our archaic gutmicrobiota and, therefore, to our genome, which has changed relatively little since humans first appeared. While the exact mechanism by which the gutmicrobiota may modulate cholesterol levels still remains uncertain, end products of bacterial fermentation, particularly the short chain fatty acids (i.e., propionate), have been suggested as potential candidates. While more research is required to clarify the potential link between gutmicrobiota and CHD risk reduction, consuming a therapeutic diet rich in plant foods, dietary fiber, and fermentable substrate would be a useful strategy for improving systemic health, possibly by altering the gutmicrobiota.

The gut immune system has a key role in the development of autoimmune diabetes, and factors that control the gut immune system are also regulators of beta-cell autoimmunity. Gutmicrobiota modulate the function of the gut immune system by their effect on the innate immune system, such as the intestinal epithelial cells and dendritic cells, and on the adaptive immune system, in particular intestinal T cells. Due to the immunological link between gut and pancreas, e.g. the shared lymphocyte hom...

Gutmicrobiota consist of a variety of microorganisms which inhabit the human gut. They play many well-known roles in human gut homeostasis and may be implicated in some pathologic processes especially immunological events. Depression is a chronic syndrome with a pathogenesis linked to various genetic, biological and environmental factors. In recent years inflammatory factors has been mentioned as contributing factors for development and exacerbation of depression. Most of these inflammatory ...

Full Text Available Rheumatoid arthritis (RA is a systemic autoimmune disease, caused by both genetic and environmental factors. Recently, investigators have focused on the gutmicrobiota, which is thought to be an environmental agent affecting the development of RA. Here we review the evidence from animal and human studies that supports the role of the gutmicrobiota in RA. We and others have demonstrated that the abundance of Prevotella copri is increased in some early RA. We have also used gnotobiotic experiments to show that dysbiosis in RA patients contributed to the development of Th17 cell-dependent arthritis in intestinal microbiota-humanized SKG mice. On the other hand, Prevotella histicola from human gutmicrobiota suppressed the development of arthritis. In summary, Prevotella species are involved in the pathogenesis of arthritis.

Prebiotics are non-digestible feed ingredients that are metabolized by specific members of intestinal microbiota and provide health benefits for the host. Fermentable oligosaccharides are best known prebiotics that have received increasing attention in poultry production. They act through diverse mechanisms, such as providing nutrients, preventing pathogen adhesion to host cells, interacting with host immune systems and affecting gut morphological structure, all presumably through modulation of intestinal microbiota. Currently, fructooligosaccharides, inulin and mannanoligosaccharides have shown promising results while other prebiotic candidates such as xylooligosaccharides are still at an early development stage. Despite a growing body of evidence reporting health benefits of prebiotics in chickens, very limited studies have been conducted to directly link health improvements to prebiotic-dependent changes in the gutmicrobiota. This article visits the current knowledge of the chicken gastrointestinal microbiota and reviews most recent publications related to the roles played by prebiotics in modulation of the gutmicrobiota and immune functions. Progress in this field will help us better understand how the gutmicrobiota contributes to poultry health and productivity, and support the development of new prebiotic products as an alternative to in-feed antibiotics.

Increasing evidence indicates that the gutmicrobiota can be altered to ameliorate or prevent disease states, and engineering the gutmicrobiota to therapeutically modulate host metabolism is an emerging goal of microbiome research. In the intestine, bacterial urease converts host-derived urea to ammonia and carbon dioxide, contributing to hyperammonemia-associated neurotoxicity and encephalopathy in patients with liver disease. Here, we engineered murine gutmicrobiota to reduce urease activity. Animals were depleted of their preexisting gutmicrobiota and then inoculated with altered Schaedler flora (ASF), a defined consortium of 8 bacteria with minimal urease gene content. This protocol resulted in establishment of a persistent new community that promoted a long-term reduction in fecal urease activity and ammonia production. Moreover, in a murine model of hepatic injury, ASF transplantation was associated with decreased morbidity and mortality. These results provide proof of concept that inoculation of a prepared host with a defined gutmicrobiota can lead to durable metabolic changes with therapeutic utility.

New insight suggests gutmicrobiota as a component in energy balance. However, the underlying mechanisms by which gutmicrobiota can impact metabolic regulation is unclear. A recent study from our lab shows, for the first time, a link between gutmicrobiota and energy balance circuitries...

Irritable bowel syndrome (IBS) is a complex disorder characterized by abdominal symptoms including chronic abdominal pain or discomfort and altered bowel habits. The etiology of IBS is multifactorial, as abnormal gut motility, visceral hypersensitivity, disturbed neural function of the brain-gut axis and an abnormal autonomic nervous system are all implicated in disease progression. Based on recent experimental and clinical studies, it has been suggested that additional etiological factors including low-grade inflammation, altered gutmicrobiota and alteration in the gut immune system play important roles in the pathogenesis of IBS. Therefore, therapeutic restoration of altered intestinal microbiota may be an ideal treatment for IBS. Probiotics are live organisms that are believed to cause no harm and result in health benefits for the host. Clinical efficacy of probiotics has been shown in the treatment or prevention of some gastrointestinal inflammation-associated disorders including traveler's diarrhea, antibiotics-associated diarrhea, pouchitis of the restorative ileal pouch and necrotizing enterocolitis. The molecular mechanisms, as cause of IBS pathogenesis, affected by altered gutmicrobiota and gut inflammation-immunity are reviewed. The effect of probiotics on the gut inflammation-immune systems and the results from clinical trials of probiotics for the treatment of IBS are also summarized.

Gutmicrobiota has been recognized as an important environmental factor in health, as well as in metabolic and immunological diseases, in which perturbation of the host gutmicrobiota is often observed in the diseased state. However, little is known on the role of gutmicrobiota in systemic lupus erythematosus. We investigated the effects of host genetics, sex, age, and dietary intervention on the gut microbiome in a murine lupus model. In young, female lupus-prone mice resembling women at childbearing age, a population with the highest risk for lupus, we found marked depletion of lactobacilli, and increases in Lachnospiraceae and overall diversity compared to age-matched healthy controls. The predicted metagenomic profile in lupus-prone mice showed a significant enrichment of bacterial motility- and sporulation-related pathways. Retinoic acid as a dietary intervention restored lactobacilli that were downregulated in lupus-prone mice, and this correlated with improved symptoms. The predicted metagenomes also showed that retinoic acid reversed many lupus-associated changes in microbial functions that deviated from the control. In addition, gutmicrobiota of lupus-prone mice were different between sexes, and an overrepresentation of Lachnospiraceae in females was associated with an earlier onset of and/or more severe lupus symptoms. Clostridiaceae and Lachnospiraceae, both harboring butyrate-producing genera, were more abundant in the gut of lupus-prone mice at specific time points during lupus progression. Together, our results demonstrate the dynamics of gutmicrobiota in murine lupus and provide evidence to suggest the use of probiotic lactobacilli and retinoic acid as dietary supplements to relieve inflammatory flares in lupus patients.

Full Text Available Obesity is a serious public health issue affecting both children and adults. Prevention and management of obesity is proposed to begin in childhood when environmental factors exert a long-term effect on the risk for obesity in adulthood. Thus, identifying modifiable factors may help to reduce this risk. Recent evidence suggests that gutmicrobiota is involved in the control of body weight, energy homeostasis and inflammation and thus, plays a role in the pathophysiology of obesity. Prebiotics and probiotics are of interest because they have been shown to alter the composition of gutmicrobiota and to affect food intake and appetite, body weight and composition and metabolic functions through gastrointestinal pathways and modulation of the gut bacterial community. As shown in this review, prebiotics and probiotics have physiologic functions that contribute to changes in the composition of gutmicrobiota, maintenance of a healthy body weight and control of factors associated with childhood obesity through their effects on mechanisms controlling food intake, fat storage and alterations in gutmicrobiota.

Obesity is a serious public health issue affecting both children and adults. Prevention and management of obesity is proposed to begin in childhood when environmental factors exert a long-term effect on the risk for obesity in adulthood. Thus, identifying modifiable factors may help to reduce this risk. Recent evidence suggests that gutmicrobiota is involved in the control of body weight, energy homeostasis and inflammation and thus, plays a role in the pathophysiology of obesity. Prebiotics and probiotics are of interest because they have been shown to alter the composition of gutmicrobiota and to affect food intake and appetite, body weight and composition and metabolic functions through gastrointestinal pathways and modulation of the gut bacterial community. As shown in this review, prebiotics and probiotics have physiologic functions that contribute to changes in the composition of gutmicrobiota, maintenance of a healthy body weight and control of factors associated with childhood obesity through their effects on mechanisms controlling food intake, fat storage and alterations in gutmicrobiota.

The human gastrointestinal (GI) tract harbours a complex and dynamic population of microorganisms, the gutmicrobiota, which exert a marked influence on the host during homeostasis and disease. Multiple factors contribute to the establishment of the human gutmicrobiota during infancy. Diet is considered as one of the main drivers in shaping the gutmicrobiota across the life time. Intestinal bacteria play a crucial role in maintaining immune and metabolic homeostasis and protecting against pathogens. Altered gut bacterial composition (dysbiosis) has been associated with the pathogenesis of many inflammatory diseases and infections. The interpretation of these studies relies on a better understanding of inter-individual variations, heterogeneity of bacterial communities along and across the GI tract, functional redundancy and the need to distinguish cause from effect in states of dysbiosis. This review summarises our current understanding of the development and composition of the human GI microbiota, and its impact on gut integrity and host health, underlying the need for mechanistic studies focusing on host–microbe interactions. PMID:28512250

Tremendous progress has been made in characterizing the bidirectional interactions between the central nervous system, the enteric nervous system, and the gastrointestinal tract. A series of provocative preclinical studies have suggested a prominent role for the gutmicrobiota in these gut-brain interactions. Based on studies using rodents raised in a germ-free environment, the gutmicrobiota appears to influence the development of emotional behavior, stress- and pain-modulation systems, and brain neurotransmitter systems. Additionally, microbiota perturbations by probiotics and antibiotics exert modulatory effects on some of these measures in adult animals. Current evidence suggests that multiple mechanisms, including endocrine and neurocrine pathways, may be involved in gutmicrobiota-to-brain signaling and that the brain can in turn alter microbial composition and behavior via the autonomic nervous system. Limited information is available on how these findings may translate to healthy humans or to disease states involving the brain or the gut/brain axis. Future research needs to focus on confirming that the rodent findings are translatable to human physiology and to diseases such as irritable bowel syndrome, autism, anxiety, depression, and Parkinson's disease.

Full Text Available The Sasang constitutional medicine has long been applied to diagnose and treat patients with various diseases. Studies have been conducted for establishment of scientific evidence supporting Sasang Constitutional (SC diagnosis. Recent human microbiome studies have demonstrated individual variations of gutmicrobiota which can be dependent on lifestyle and health conditions. We hypothesized that gut microbial similarities and discrepancies may exist across SC types. We compared the difference of gutmicrobiota among three constitutions (So-Yang, So-Eum, and Tae-Eum, along with the investigation of anthropometric and biochemical parameters. Firmicutes and Bacteroidetes were predominant phyla in all SC types. The median plot analysis suggested that Firmicutes and Bacteroidetes appeared more abundant in SE and TE, respectively, in the male subjects of 20–29 years old. At the genus level, Bifidobacterium and Bacteroides manifested the difference between SE and TE types. For anthropometry, body weight, body mass index, and waist circumference of the TE type were significantly higher than those of the other types. Overall, findings indicated a possible link between SC types and gutmicrobiota within a narrow age range. Further investigations are deemed necessary to elucidate the influences of age, gender, and other factors in the context of SC types and gutmicrobiota.

Obesity develops from a prolonged imbalance of energy intake and energy expenditure. However, the relatively recent discovery that the composition and function of the gutmicrobiota impacts on obesity has lead to an explosion of interest in what is now a distinct research field. Here, research relating to the links between the gutmicrobiota, diet and obesity will be reviewed under five major headings: (1) the gutmicrobiota of lean and obese animals, (2) the composition of the gutmicrobiota of lean and obese humans, (3) the impact of diet on the gutmicrobiota, (4) manipulating the gutmicrobiota and (5) the mechanisms by which the gutmicrobiota can impact on weight gain. PMID:22572830

for neurodevelopment and mental health. These diverse multisystem influences have sparked interest in strategies that might favorably modulate the gutmicrobiota to reduce the risk of many NCDs. For example, specific prebiotics promote favorable intestinal colonization, and their fermented products have anti...

Full Text Available The human digestive system harbors a diverse and complex community of microorganisms that work in a symbiotic fashion with the host, contributing to metabolism, immune response and intestinal architecture. However, disruption of a stable and diverse community, termed “dysbiosis”, has been shown to have a profound impact upon health and disease. Emerging data demonstrate dysbiosis of the gutmicrobiota to be linked with non-alcoholic fatty liver disease (NAFLD. Although the exact mechanism(s remain unknown, inflammation, damage to the intestinal membrane, and translocation of bacteria have all been suggested. Lifestyle intervention is undoubtedly effective at improving NAFLD, however, not all patients respond to these in the same manner. Furthermore, studies investigating the effects of lifestyle interventions on the gutmicrobiota in NAFLD patients are lacking. A deeper understanding of how different aspects of lifestyle (diet/nutrition/exercise affect the host–microbiome interaction may allow for a more tailored approach to lifestyle intervention. With gutmicrobiota representing a key element of personalized medicine and nutrition, we review the effects of lifestyle interventions (diet and physical activity/exercise on gutmicrobiota and how this impacts upon NAFLD prognosis.

Over the last 10-15 years, our understanding of the composition and functions of the human gutmicrobiota has increased exponentially. To a large extent, this has been due to new 'omic' technologies that have facilitated large-scale analysis of the genetic and metabolic profile of this microbial

Gutmicrobiota plays an important role in cirrhosis. The liver is constantly challenged with commensal bacteria and their products arriving through the portal vein in the so-called gut-liver axis. Bacterial translocation from the intestinal lumen through the intestinal wall and to mesenteric lymph nodes is facilitated by intestinal bacterial overgrowth, impairment in the permeability of the intestinal mucosal barrier, and deficiencies in local host immune defences. Deranged clearance of endogenous bacteria from portal and systemic circulation turns the gut into the major source of bacterial-related complications. Liver function may therefore be affected by alterations in the composition of the intestinal microbiota and a role for commensal flora has been evidenced in the pathogenesis of several complications arising in end-stage liver disease such as hepatic encephalopathy, splanchnic arterial vasodilatation and spontaneous bacterial peritonitis. The use of antibiotics is the main therapeutic pipeline in the management of these bacteria-related complications. However, other strategies aimed at preserving intestinal homeostasis through the use of pre-, pro- or symbiotic formulations are being studied in the last years. In this review, the role of intestinal microbiota in the development of the most frequent complications arising in cirrhosis and the different clinical and experimental studies conducted to prevent or improve these complications by modifying the gutmicrobiota composition are summarized.

The human digestive system harbors a diverse and complex community of microorganisms that work in a symbiotic fashion with the host, contributing to metabolism, immune response and intestinal architecture. However, disruption of a stable and diverse community, termed "dysbiosis", has been shown to have a profound impact upon health and disease. Emerging data demonstrate dysbiosis of the gutmicrobiota to be linked with non-alcoholic fatty liver disease (NAFLD). Although the exact mechanism(s) remain unknown, inflammation, damage to the intestinal membrane, and translocation of bacteria have all been suggested. Lifestyle intervention is undoubtedly effective at improving NAFLD, however, not all patients respond to these in the same manner. Furthermore, studies investigating the effects of lifestyle interventions on the gutmicrobiota in NAFLD patients are lacking. A deeper understanding of how different aspects of lifestyle (diet/nutrition/exercise) affect the host-microbiome interaction may allow for a more tailored approach to lifestyle intervention. With gutmicrobiota representing a key element of personalized medicine and nutrition, we review the effects of lifestyle interventions (diet and physical activity/exercise) on gutmicrobiota and how this impacts upon NAFLD prognosis.

The human digestive system harbors a diverse and complex community of microorganisms that work in a symbiotic fashion with the host, contributing to metabolism, immune response and intestinal architecture. However, disruption of a stable and diverse community, termed “dysbiosis”, has been shown to have a profound impact upon health and disease. Emerging data demonstrate dysbiosis of the gutmicrobiota to be linked with non-alcoholic fatty liver disease (NAFLD). Although the exact mechanism(s) remain unknown, inflammation, damage to the intestinal membrane, and translocation of bacteria have all been suggested. Lifestyle intervention is undoubtedly effective at improving NAFLD, however, not all patients respond to these in the same manner. Furthermore, studies investigating the effects of lifestyle interventions on the gutmicrobiota in NAFLD patients are lacking. A deeper understanding of how different aspects of lifestyle (diet/nutrition/exercise) affect the host–microbiome interaction may allow for a more tailored approach to lifestyle intervention. With gutmicrobiota representing a key element of personalized medicine and nutrition, we review the effects of lifestyle interventions (diet and physical activity/exercise) on gutmicrobiota and how this impacts upon NAFLD prognosis. PMID:27023533

Malnutrition is the result of an inadequate balance between energy intake and energy expenditure that ultimately leads to either obesity or undernutrition. Several factors are associated with the onset and preservation of malnutrition. One of these factors is the gutmicrobiota, which has been

Over the last 10-15 years, our understanding of the composition and functions of the human gutmicrobiota has increased exponentially. To a large extent, this has been due to new 'omic' technologies that have facilitated large-scale analysis of the genetic and metabolic profile of this microbial

Malnutrition is the result of an inadequate balance between energy intake and energy expenditure that ultimately leads to either obesity or undernutrition. Several factors are associated with the onset and preservation of malnutrition. One of these factors is the gutmicrobiota, which has been recog

Malnutrition is the result of an inadequate balance between energy intake and energy expenditure that ultimately leads to either obesity or undernutrition. Several factors are associated with the onset and preservation of malnutrition. One of these factors is the gutmicrobiota, which has been recog

The gutmicrobiota acts as a real organ. The symbiotic interactions between resident micro-organisms and the digestive tract highly contribute to maintain the gut homeostasis. However, alterations to the microbiome caused by environmental changes (e.g., infection, diet and/or lifestyle) can disturb this symbiotic relationship and promote disease, such as inflammatory bowel diseases and cancer. Colorectal cancer is a complex association of tumoral cells, non-neoplastic cells and a large amount of micro-organisms, and the involvement of the microbiota in colorectal carcinogenesis is becoming increasingly clear. Indeed, many changes in the bacterial composition of the gutmicrobiota have been reported in colorectal cancer, suggesting a major role of dysbiosis in colorectal carcinogenesis. Some bacterial species have been identified and suspected to play a role in colorectal carcinogenesis, such as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, Enterococcus faecalis, Clostridium septicum, Fusobacterium spp. and Escherichia coli. The potential pro-carcinogenic effects of these bacteria are now better understood. In this review, we discuss the possible links between the bacterial microbiota and colorectal carcinogenesis, focusing on dysbiosis and the potential pro-carcinogenic properties of bacteria, such as genotoxicity and other virulence factors, inflammation, host defenses modulation, bacterial-derived metabolism, oxidative stress and anti-oxidative defenses modulation. We lastly describe how bacterial microbiota modifications could represent novel prognosis markers and/or targets for innovative therapeutic strategies. PMID:26811603

The gutmicrobiota acts as a real organ. The symbiotic interactions between resident micro-organisms and the digestive tract highly contribute to maintain the gut homeostasis. However, alterations to the microbiome caused by environmental changes (e.g., infection, diet and/or lifestyle) can disturb this symbiotic relationship and promote disease, such as inflammatory bowel diseases and cancer. Colorectal cancer is a complex association of tumoral cells, non-neoplastic cells and a large amount of micro-organisms, and the involvement of the microbiota in colorectal carcinogenesis is becoming increasingly clear. Indeed, many changes in the bacterial composition of the gutmicrobiota have been reported in colorectal cancer, suggesting a major role of dysbiosis in colorectal carcinogenesis. Some bacterial species have been identified and suspected to play a role in colorectal carcinogenesis, such as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, Enterococcus faecalis, Clostridium septicum, Fusobacterium spp. and Escherichia coli. The potential pro-carcinogenic effects of these bacteria are now better understood. In this review, we discuss the possible links between the bacterial microbiota and colorectal carcinogenesis, focusing on dysbiosis and the potential pro-carcinogenic properties of bacteria, such as genotoxicity and other virulence factors, inflammation, host defenses modulation, bacterial-derived metabolism, oxidative stress and anti-oxidative defenses modulation. We lastly describe how bacterial microbiota modifications could represent novel prognosis markers and/or targets for innovative therapeutic strategies.

Surgery involving the gastrointestinal tract continues to prove challenging because of the persistence of unpredictable complications such as anastomotic leakage and life-threatening infections. Removal of diseased intestinal segments results in substantial catabolic stress and might require complex reconstructive surgery to maintain the functional continuity of the intestinal tract. As gastrointestinal surgery necessarily involves a breach of an epithelial barrier colonized by microorganisms, preoperative intestinal antisepsis is used to reduce infection-related complications. The current approach to intestinal antisepsis varies widely across institutions and countries with little understanding of its mechanism of action, effect on the gutmicrobiota and overall efficacy. Many of the current approaches to intestinal antisepsis before gastrointestinal surgery run counter to emerging concepts of intestinal microbiota contributing to immune function and recovery from injury. Here, we review evidence outlining the role of gutmicrobiota in recovery from gastrointestinal surgery, particularly in the development of infections and anastomotic leak. To make surgery safer and further reduce complications, a molecular, genetic and functional understanding of the response of the gastrointestinal tract to alterations in its microbiota is needed. Methods can then be developed to preserve the health-promoting functions of the microbiota while at the same time suppressing their harmful effects.

The advent of vaccination and improved hygiene have eliminated many of the deadly infectious pathogens in developed nations. However, the incidences of inflammatory diseases, such as inflammatory bowel disease, asthma, obesity and diabetes are increasing dramatically. Research in the recent decades revealed that it is indeed the lack of early childhood microbial exposure, increase use of antibiotics, as well as increase consumption of processed foods high in carbohydrates and fats, and lacking fibre, which wreak havoc on the proper development of immunity and predispose the host to elevated inflammatory conditions. Although largely unexplored and under-appreciated until recent years, these factors impact significantly on the composition of the gutmicrobiota (a collection of microorganisms that live within the host mucosal tissue) and inadvertently play intricate and pivotal roles in modulating an appropriate host immune response. The suggestion that shifts in the composition of host microbiota is a risk factor for inflammatory disease raises an exciting opportunity whereby the microbiota may also present as a potential modifiable component or therapeutic target for inflammatory diseases. This review provides insights into the interactions between the microbiota and the immune system, how these affect disease phenotypes, and explore current and emerging therapies that target the gutmicrobiota as potential treatment for inflammatory diseases. PMID:27195115

Rheumatoid arthritis (RA) is a systemic, inflammatory, and autoimmune disorder. Gutmicrobiota play an important role in the etiology of RA. With the considerable progress made in next-generation sequencing techniques, the identified gutmicrobiota difference between RA patients and healthy individuals provides an updated overview of the association between gutmicrobiota and RA. We reviewed the reported correlation and underlying molecular mechanisms among gutmicrobiota, the immune system, and RA. It has become known that gutmicrobiota contribute to the pathogenesis of RA via multiple molecular mechanisms. The progressive understanding of the dynamic interaction between gutmicrobiota and their host will help in establishing a highly individualized management for each RA patient, and achieve a better efficacy in clinical practice, or even discovering new drugs for RA.

The anoxic saccharide-rich conditions of the earthwormgut provide an ideal transient habitat for ingested microbes capable of anaerobiosis. It was recently discovered that the earthworm Eudrilus eugeniae from Brazil can emit methane (CH4) and that ingested methanogens might be associated with this

Diabetes is a condition of multifactorial origin, involving several molecular mechanisms related to the intestinal microbiota for its development. In type 2 diabetes, receptor activation and recognition by microorganisms from the intestinal lumen may trigger inflammatory responses, inducing the phosphorylation of serine residues in insulin receptor substrate-1, reducing insulin sensitivity. In type 1 diabetes, the lowered expression of adhesion proteins within the intestinal epithelium favour...

There is growing evidence that dysbiosis of the gutmicrobiota is associated with the pathogenesis of both intestinal and extra-intestinal disorders. Intestinal disorders include inflammatory bowel disease, irritable bowel syndrome (IBS), and coeliac disease, while extra-intestinal disorders include allergy, asthma, metabolic syndrome, cardiovascular disease, and obesity.In many of these conditions, the mechanisms leading to disease development involves the pivotal mutualistic relationship be...

Full Text Available BACKGROUND: The prevalence of obesity and related disorders such as metabolic syndrome and diabetes has vastly increased throughout the world. Recent insights have generated an entirely new perspective suggesting that our microbiota might be involved in the development of these disorders. This represents an area of scientific need, opportunity and challenge. The insights gleaned should help to address several pressing global health problems. CONTENT: Our bowels have two major roles: the digestion and absorption of nutrients and the maintenance of a barrier against the external environment. They fulfill these functions in the context of, and with the help from, tens of trillions of resident microbes, known as the gutmicrobiota. Studies have demonstrated that obesity and metabolic syndrome may be associated with profound microbiotal changes, and the induction of a metabolic syndrome phenotype through fecal transplants corroborates the important role of the microbiota in this disease. Dietary composition and caloric intake appear to swiftly regulate intestinal microbial composition and function. SUMMARY: The interaction of the intestinal microbial world with its host, and its mutual regulation, will become one of the important topics of biomedical research and will provide us with further insights at the interface of microbiota, metabolism, metabolic syndrome, and obesity. A better understanding of the interaction between certain diets and the human gut microbiome should help to develop new guidelines for feeding humans at various time points in their life, help to improve global human health, and establish ways to prevent or treat various food-related diseases. KEYWORDS: gutmicrobiota, obesity, metabolic syndrome, type 2 diabetes.

Background: Gutmicrobiota is considered as a major regulator of metabolic disease. This reconciles the notion of metabolic inflammation and the epidemic development of the disease. In addition to evidence showing that a specific gutmicrobiota characterizes patients with obesity, type 2 diabetes, and hepatic steatosis, the mechanisms causal to the disease could be related to the translocation of microbiota from the gut to the tissues, inducing inflammation. The mechanisms regulating such a p...

Type 1 Diabetes (T1D) is a multifactorial, immune-mediated disease, which is characterized by the progressive destruction of autologous insulin-producing beta cells in the pancreas. The risk of developing T1D is determined by genetic, epigenetic and environmental factors. In the past few decades there has been a continuous rise in the incidence of T1D, which cannot be explained by genetic factors alone. Changes in our lifestyle that include diet, hygiene, and antibiotic usage have already been suggested to be causal factors for this rising T1D incidence. Only recently have microbiota, which are affected by all these factors, been recognized as key environmental factors affecting T1D development. In this review we will summarize current knowledge on the impact of gutmicrobiota on T1D development and give an outlook on the potential to design new microbiota-based therapies in the prevention and treatment of T1D.

Full Text Available There is growing evidence that dysbiosis of the gutmicrobiota is associated with the pathogenesis of both intestinal and extra-intestinal disorders. Intestinal disorders include inflammatory bowel disease, irritable bowel syndrome (IBS, and coeliac disease, while extra-intestinal disorders include allergy, asthma, metabolic syndrome, cardiovascular disease, and obesity.In many of these conditions, the mechanisms leading to disease development involves the pivotal mutualistic relationship between the colonic microbiota, their metabolic products, and the host immune system. The establishment of a ‘healthy’ relationship early in life appears to be critical to maintaining intestinal homeostasis. Whilst we do not yet have a clear understanding of what constitutes a ‘healthy’ colonic microbiota, a picture is emerging from many recent studies identifying particular bacterial species associated with a healthy microbiota. In particular, the bacterial species residing within the mucus layer of the colon, either through direct contact with host cells, or through indirect communication via bacterial metabolites, may influence whether host cellular homeostasis is maintained or whether inflammatory mechanisms are triggered. In addition to inflammation, there is some evidence that perturbations in the gutmicrobiota is involved with the development of colorectal cancer. In this case, dysbiosis may not be the most important factor, rather the products of interaction between diet and the microbiome. High-protein diets are thought to result in the production of carcinogenic metabolites from the colonic microbiota that may result in the induction of neoplasia in the colonic epithelium.Ever more sensitive metabolomics methodologies reveal a suite of small molecules produced in the microbiome which mimic or act as neurosignallers or neurotransmitters. Coupled with evidence that probiotic interventions may alter psychological endpoints in both humans and in

Full Text Available The composition of human gutmicrobiota and their relationship with the host and, consequently, with human health and disease, presents several challenges to microbiologists. Originally dominated by culture-dependent methods for exploring this ecosystem, the advent of molecular tools has revolutionized our ability to investigate these relationships. However, many biases that have led to contradictory results have been identified. Microbial culturomics, a recent concept based on a use of several culture conditions with identification by MALDI-TOF followed by the genome sequencing of the new species cultured had allowed a complementarity with metagenomics. Culturomics allowed to isolate 31 new bacterial species the largest human virus, the largest bacteria, and the largest Archaea from human. Moreover, some members of this ecosystem, such as Eukaryotes, giant viruses, Archaea and Planctomycetes, have been neglected by the majority of studies. In addition, numerous factors, such as age, geographic provenance, dietary habits, antibiotics or probiotics, can influence the composition of the microbiota. Finally, in addition to the countless biases associated with the study techniques, a considerable limitation to the interpretation of studies of human gutmicrobiota is associated with funding sources and transparency disclosures. In the future, studies independent of food industry funding and using complementary methods from a broad range of both culture-based and molecular tools will increase our knowledge of the repertoire of this complex ecosystem and host-microbiota mutualism.

The incidence of diabetes has increased rapidly across the entire world in the last 2 decades. Accumulating evidence suggests that gutmicrobiota contribute to the pathogenesis of diabetes. Several studies have demonstrated that patients with diabetes are characterized by a moderate degree of gut microbial dysbiosis. However, there are still substantial controversies regarding altered composition of the gutmicrobiota and the underlying mechanisms by which gutmicrobiota interact with the body's metabolism. The purpose of this review is to define the association between gutmicrobiota and diabetes. In doing so an electronic search of studies published in English from January 2004 to the November 2014 in the National Library of Medicine, including the original studies that addressed the effects of gutmicrobiota on diabetes, energy metabolism, inflammation, the immune system, gut permeability and insulin resistance, was performed. Herein, we discuss the possible mechanisms by which the gutmicrobiota are involved in the development of diabetes, including energy metabolism, inflammation, the innate immune system, and the bowel function of the intestinal barrier. The compositional changes in the gutmicrobiota in type 2 and type 1 diabetes are also discussed. Moreover, we introduce the new findings of fecal transplantation, and use of probiotics and prebiotics as new treatment strategies for diabetes. Future research should be focused on defining the primary species of the gutmicrobiota and their exact roles in diabetes, potentially increasing the possibility of fecal transplants as a therapeutic strategy for diabetes.

Rapid environmental transition and modern lifestyles are likely driving changes in the biodiversity of the human gutmicrobiota. With clear effects on physiologic, immunologic, and metabolic processes in human health, aberrations in the gut microbiome and intestinal homeostasis have the capacity for multisystem effects. Changes in microbial composition are implicated in the increasing propensity for a broad range of inflammatory diseases, such as allergic disease, asthma, inflammatory bowel disease (IBD), obesity, and associated noncommunicable diseases (NCDs). There are also suggestive implications for neurodevelopment and mental health. These diverse multisystem influences have sparked interest in strategies that might favorably modulate the gutmicrobiota to reduce the risk of many NCDs. For example, specific prebiotics promote favorable intestinal colonization, and their fermented products have anti-inflammatory properties. Specific probiotics also have immunomodulatory and metabolic effects. However, when evaluated in clinical trials, the effects are variable, preliminary, or limited in magnitude. Fecal microbiota transplantation is another emerging therapy that regulates inflammation in experimental models. In human subjects it has been successfully used in cases of Clostridium difficile infection and IBD, although controlled trials are lacking for IBD. Here we discuss relationships between gut colonization and inflammatory NCDs and gutmicrobiota modulation strategies for their treatment and prevention.

The gastrointestinal (GI) ecosystem is increasingly understood to be a fundamental component of health, and has been identified as a new focal point for diagnosing, correcting and preventing countless disorders. Shotgun DNA sequencing has emerged as the dominant technology for determining the genetic and microbial composition of the gutmicrobiota. This technology has linked microbiota dysbioses to numerous GI diseases including inflammatory bowel disease, obesity and allergy, and to non-GI diseases like autism and depression. The importance of establishing causality in the deterioration of the host-microbiota relationship is well appreciated; however, discovery of candidate molecules and pathways that underlie mechanisms remains a major challenge. Targeted approaches, transcriptional assays, cytokine panels and imaging analyses, applied to animals, have yielded important insight into host responses to the microbiota. However, non-invasive, hypothesis-independent means of measuring host responses in humans are necessary to keep pace with similarly unbiased sequencing efforts that monitor microbes. Mass spectrometry-based proteomics has served this purpose in many other fields, but stool proteins exist in such diversity and dynamic range as to overwhelm conventional proteomics technologies. Focused analysis of host protein secretion into the gut lumen and monitoring proteome-level dynamics in stool provides a tractable route toward non-invasively evaluating dietary, microbial, surgical or pharmacological intervention efficacies. This review is intended to guide GI biologists and clinicians through the methods currently used to elucidate host responses in the gut, with a specific focus on mass spectrometry-based shotgun proteomics applied to the study of host protein dynamics within the GI ecosystem.

The human oro-gastrointestinal (GI) tract is a complex system, consisting of oral cavity, pharynx, oesophagus, stomach, small intestine, large intestine, rectum and anus, which all together with the accessory digestive organs constitute the digestive system. The function of the digestive system is to break down dietary constituents into small molecules and then absorb these for subsequent distribution throughout the body. Besides digestion and carbohydrate metabolism, the indigenous microbiota has an important influence on host physiological, nutritional and immunological processes, and commensal bacteria are able to modulate the expression of host genes that regulate diverse and fundamental physiological functions. The main external factors that can affect the composition of the microbial community in generally healthy adults include major dietary changes and antibiotic therapy. Changes in some selected bacterial groups have been observed due to controlled changes to the normal diet e.g. high-protein diet, high-fat diet, prebiotics, probiotics and polyphenols. More specifically, changes in the type and quantity of non-digestible carbohydrates in the human diet influence both the metabolic products formed in the lower regions of the GI tract and the bacterial populations detected in faeces. The interactions between dietary factors, gutmicrobiota and host metabolism are increasingly demonstrated to be important for maintaining homeostasis and health. Therefore the aim of this review is to summarise the effect of diet, and especially dietary interventions, on the human gutmicrobiota. Furthermore, the most important confounding factors (methodologies used and intrinsic human factors) in relation to gutmicrobiota analyses are elucidated.

This thesis supports the hypothesis that gutmicrobiota can be viewed as an ‘exteriorised organ’ that contributes to energy metabolism and the modulation of our immune system. Following Koch’s postulates, it has now been shown that gutmicrobiota are associated with metabolic disease and that these

This thesis supports the hypothesis that gutmicrobiota can be viewed as an ‘exteriorised organ’ that contributes to energy metabolism and the modulation of our immune system. Following Koch’s postulates, it has now been shown that gutmicrobiota are associated with metabolic disease and that these

Gutmicrobiota have been implicated as a relevant factor in the development of type 2 diabetes mellitus (T2DM), and its diversity might be a cause of variation in animal models of T2DM. In this study, we aimed to characterise the gutmicrobiota of a T2DM mouse model with a long term vision of bei...

Introduction: Advances in tools for molecular investigations have allowed deeper understanding of how microbes can influence host physiology. A very interesting field of research that has gained attention recently is the possible role of gutmicrobiota in the development of obesity and metabolic disorders. Objective: The aim of this review is to discuss mechanisms that explain the influence of gutmicrobiota on host metabolism. Results and discussion: The gutmicrobiota is important for norma...

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder affecting 1 in 10,000 live female births. Changes in microbiota composition, as observed in other neurological disorders such as autism spectrum disorders, may account for several symptoms typically associated with RTT. We studied the relationship between disease phenotypes and microbiome by analyzing diet, gutmicrobiota, and short-chain fatty acid (SCFA) production. We enrolled eight RTT patients and 10 age- and sex-matched healthy women, all without dietary restrictions. The microbiota was characterized by 16S rRNA gene sequencing, and SCFAs concentration was determined by gas chromatographic analysis. The RTT microbiota showed a lower α diversity, an enrichment in Bacteroidaceae, Clostridium spp., and Sutterella spp., and a slight depletion in Ruminococcaceae. Fecal SCFA concentrations were similar, but RTT samples showed slightly higher concentrations of butyrate and propionate, and significant higher levels in branched-chain fatty acids. Daily caloric intake was similar in the two groups, but macronutrient analysis showed a higher protein content in RTT diets. Microbial function prediction suggested in RTT subjects an increased number of microbial genes encoding for propionate and butyrate, and amino acid metabolism. A full understanding of these critical features could offer new, specific strategies for managing RTT-associated symptoms, such as dietary intervention or pre/probiotic supplementation. PMID:28178201

Full Text Available Rett syndrome (RTT is an X-linked neurodevelopmental disorder affecting 1 in 10,000 live female births. Changes in microbiota composition, as observed in other neurological disorders such as autism spectrum disorders, may account for several symptoms typically associated with RTT. We studied the relationship between disease phenotypes and microbiome by analyzing diet, gutmicrobiota, and short-chain fatty acid (SCFA production. We enrolled eight RTT patients and 10 age- and sex-matched healthy women, all without dietary restrictions. The microbiota was characterized by 16S rRNA gene sequencing, and SCFAs concentration was determined by gas chromatographic analysis. The RTT microbiota showed a lower α diversity, an enrichment in Bacteroidaceae, Clostridium spp., and Sutterella spp., and a slight depletion in Ruminococcaceae. Fecal SCFA concentrations were similar, but RTT samples showed slightly higher concentrations of butyrate and propionate, and significant higher levels in branched-chain fatty acids. Daily caloric intake was similar in the two groups, but macronutrient analysis showed a higher protein content in RTT diets. Microbial function prediction suggested in RTT subjects an increased number of microbial genes encoding for propionate and butyrate, and amino acid metabolism. A full understanding of these critical features could offer new, specific strategies for managing RTT-associated symptoms, such as dietary intervention or pre/probiotic supplementation.

Infections have been linked to the development of cardiovascular disease and atherosclerosis. Findings from the past decade have identified microbial ecosystems residing in different habitats of the human body that contribute to metabolic and cardiovascular-related disorders. In this Review, we...... of atherosclerotic plaques. Third, diet and specific components that are metabolized by gutmicrobiota can have various effects on atherosclerosis; for example, dietary fibre is beneficial, whereas the bacterial metabolite trimethylamine-N-oxide is considered harmful. Although specific bacterial taxa have been...... associated with atherosclerosis, which is supported by increasing mechanistic evidence, several questions remain to be answered to understand fully how the microbiota contributes to atherosclerosis and cardiovascular disease. Such knowledge might pave the way for novel diagnostics and therapeutics based...

The global prevalence of obesity and related comorbidities has increased considerably over the past decades. In addition to an increase in food consumption and a reduction in physical activity, growing evidence implicates the microorganisms in our gastrointestinal tract, referred to as the gutmicrobiota, in obesity and related metabolic disturbances. The composition of the gutmicrobiota can fluctuate markedly within an individual and between individuals. Changes in gut microbial composition may be unfavorable and predispose an individual to disease. Studies in mice that are germ free, mice that are cohoused, and mice that are treated with antibiotics have provided some evidence that changes in gutmicrobiota may causally contribute to metabolic disorders. Several mechanisms have been proposed and explored that may mediate the effects of the gutmicrobiota on metabolic disorders. In this review, we carefully analyze the literature on the connection between the gutmicrobiota and metabolic health, with a focus on studies demonstrating a causal relation and clarifying potential underlying mechanisms. Despite a growing appreciation for a role of the gutmicrobiota in metabolic health, more experimental evidence is needed to substantiate a cause-and-effect relationship. If a clear causal relationship between the gutmicrobiota and metabolic health can be established, dietary interventions can be targeted toward improving gut microbial composition in the prevention and perhaps even the treatment of metabolic diseases.

The concept that the gutmicrobiota serves as a virtual endocrine organ arises from a number of important observations. Evidence for a direct role arises from its metabolic capacity to produce and regulate multiple compounds that reach the circulation and act to influence the function of distal organs and systems. For example, metabolism of carbohydrates results in the production of short-chain fatty acids, such as butyrate and propionate, which provide an important source of nutrients as well as regulatory control of the host digestive system. This influence over host metabolism is also seen in the ability of the prebiotic inulin to influence production of relevant hormones such as glucagon-like peptide-1, peptide YY, ghrelin, and leptin. Moreover, the probiotic Lactobacillus rhamnosus PL60, which produces conjugated linoleic acid, has been shown to reduce body-weight gain and white adipose tissue without effects on food intake. Manipulating the microbial composition of the gastrointestinal tract modulates plasma concentrations of tryptophan, an essential amino acid and precursor to serotonin, a key neurotransmitter within both the enteric and central nervous systems. Indirectly and through as yet unknown mechanisms, the gutmicrobiota exerts control over the hypothalamic-pituitary-adrenal axis. This is clear from studies on animals raised in a germ-free environment, who show exaggerated responses to psychological stress, which normalizes after monocolonization by certain bacterial species including Bifidobacterium infantis. It is tempting to speculate that therapeutic targeting of the gutmicrobiota may be useful in treating stress-related disorders and metabolic diseases. PMID:24892638

The “microbial world within us” (Zoetendal et al., 2006) is populated by a complex society of indigenous microorganisms that feature different “ethnic” populations. Those microbial cells thriving within us are estimated to outnumber human body cells by a factor of ten to one. Insights into the relation between the intestinal microbial community and its host have been gained through gnotobiology. Indeed, the influence of the gutmicrobiota upon human development, physiology, immunity, and nutrition has been inferred by comparing gnotoxenic and axenic murine models (Hooper et al., 1998, 2002, 2003; Hooper and Gordon, 2001).

Full Text Available The intestine habitat is the natural collection of symbiotic microorganisms. The bacterial population enables many permanent metabolic activities in this environment. Inside the intestine of mammals there are an extended genome of millions of bacterial genes named microbiome. In recent years, there has been an increased interest of scientists to discover the place and the role of bio-ecological content and modulation of gutmicrobiota in a host organism using prebiotics, probiotics and synbiotics, which may have a great benefit for human health. [Projekat Ministarstva nauke Republike Srbije, br. 46012 i br. 41012

New gene sequencing-based techniques and the large worldwide sequencing capacity have introduced a new era within the field of gutmicrobiota. Animal and human studies have shown that obesity and type 2 diabetes are associated with changes in the composition of the gutmicrobiota...... and that prebiotics, antibiotics or faecal transplantation can alter glucose and lipid metabolism. This paper summarizes the latest research regarding the association between gutmicrobiota, diabetes and obesity and some of the mechanisms by which gut bacteria may influence host metabolism....

The human microbiota consists of a complex community of microbial cells that live on and inside each person in a close relationship with their host. The majority of the microbial cells are harboured by the gastro intestinal tract where 10-100 trillion bacteria reside. The microbiota is a dynamic...... community where both composition and function can be affected by changes in the local environment. With the microbiota containing ~150 times more genes than the human host, the microbiota provides a large modifiable “secondary genome” (metagenome). Within the last decade, changes in the gutmicrobiota...... composition has indeed been established as a factor contributing to the health of the host. Therefore, being able to understand, control and modify the gutmicrobiota is a promising way of improving health. The following thesis is based on four different projects investigating the murine gutmicrobiota...

Neuropeptides are important mediators both within the nervous system and between neurons and other cell types. Neuropeptides such as substance P, calcitonin gene-related peptide and neuropeptide Y (NPY), vasoactive intestinal polypeptide, somatostatin and corticotropin-releasing factor are also likely to play a role in the bidirectional gut-brain communication. In this capacity they may influence the activity of the gastrointestinal microbiota and its interaction with the gut-brain axis. Current efforts in elucidating the implication of neuropeptides in the microbiota-gut-brain axis address four information carriers from the gut to the brain (vagal and spinal afferent neurons; immune mediators such as cytokines; gut hormones; gutmicrobiota-derived signalling molecules) and four information carriers from the central nervous system to the gut (sympathetic efferent neurons; parasympathetic efferent neurons; neuroendocrine factors involving the adrenal medulla; neuroendocrine factors involving the adrenal cortex). Apart from operating as neurotransmitters, many biologically active peptides also function as gut hormones. Given that neuropeptides and gut hormones target the same cell membrane receptors (typically G protein-coupled receptors), the two messenger roles often converge in the same or similar biological implications. This is exemplified by NPY and peptide YY (PYY), two members of the PP-fold peptide family. While PYY is almost exclusively expressed by enteroendocrine cells, NPY is found at all levels of the gut-brain and brain-gut axis. The function of PYY-releasing enteroendocrine cells is directly influenced by short chain fatty acids generated by the intestinal microbiota from indigestible fibre, while NPY may control the impact of the gutmicrobiota on inflammatory processes, pain, brain function and behaviour. Although the impact of neuropeptides on the interaction between the gutmicrobiota and brain awaits to be analysed, biologically active peptides

Hashimoto's thyroiditis is an organ-specific autoimmune disease in which both genetic predisposition and environmental factors serve as the trigger of the disease. A growing body of evidence suggests involvement of viral infection in the development of Hashimoto's thyroiditis. However, not only pathogenic microorganisms but also non-pathogenic commensal microorganisms induce proinflammatory or regulatory immune responses within the host. In accordance, series of studies indicate a critical role of intestinal commensal microbiota in the development of autoimmune diseases including inflammatory bowel diseases, type 1 diabetes, rheumatoid arthritis, and multiple sclerosis. In contrast, the role of the gut and indigenous microorganisms in Hashimoto's thyroiditis has received little attention. Whereas activation of innate pattern recognition receptors such as Toll-like receptors and disturbed intestinal epithelial barrier may contribute to thyroiditis development, only a few studies have addressed a link between the gut and Hashimoto's thyroiditis and provided just indirect and weak evidence for such a link. Despite this unsatisfactory situation, we here focus on the possible interaction between the gut and thyroid autoimmunity. Further studies are clearly needed to test the hypothesis that the gut commensal microflora represents an important environmental factor triggering Hashimoto's thyroiditis.

Non-steroidal anti-inflammatory drugs (NSAIDs) can cause significant small bowel injuries. The role of gutmicrobiota in this NSAID-induced enteropathy is poorly understood. We studied the dynamic changes in gutmicrobiota following indomethacin administration in mice, and investigated the effects of these adaptive changes on subsequent NSAID-induced enteropathy. The changes in gutmicrobiota were studied using 16S rRNA sequencing, and the effects of such changes were investigated using antibiotics and a faecal transplantation model. After indomethacin treatment, significant adaptive changes in gutmicrobiota were observed, including increased abundance of Firmicutes and decreased abundance in that of Bacteroidetes. Depletion of gutmicrobiota with antibiotics led to a higher mortality (P = 0.0021) in mice compared to controls. Mice pre-transplanted with adaptively changed microbiota showed less small bowel injury and lower levels of pro-inflammatory cytokines when exposed to indomethacin. In summary, this study identifies adaptive changes in the gutmicrobiota upon indomethacin administration, which can in turn ameliorate further NSAID-induced injury. The heightened mortality with antibiotic depletion of the adaptively changed microbiota suggests its important role in protecting against such injury. This study provides insight for future efforts to target the microbiota as a therapeutic strategy. PMID:28067296

Human beings harbor gut microbial communities that are essential to preserve human health. Molded by the human genome, the gutmicrobiota is an adaptive component of the human superorganisms that allows host adaptation at different timescales, optimizing host physiology from daily life to lifespan scales and human evolutionary history. The gutmicrobiota continuously changes from birth up to the most extreme limits of human life, reconfiguring its metagenomic layout in response to daily varia...

Obesity, a global epidemic of the modern era, is a risk factor for cardiovascular diseases (CVD) and diabetes. The pervasiveness of obesity and overweight in both developed as well as developing populations is on the rise and placing a huge burden on health and economic resources. Consequently, research to control this emerging epidemic is of utmost importance. Recently, host interactions with their resident gutmicrobiota (GM) have been reported to be involved in the pathogenesis of many metabolic diseases, including obesity, diabetes, and CVD. Around 10(14) microorganisms reside within the lower human intestine and many of these 10(14) microorganisms have developed mutualistic or commensal associations with the host and actively involved in many physiological processes of the host. However, dysbiosis (altered gut microbial composition) with other predisposing genetic and environmental factors, may contribute to host metabolic disorders resulting in many ailments. Therefore, delineating the role of GM as a contributing factor to obesity is the main objective of this review. Obesity research, as a field is expanding rapidly due to major advances in nutrigenomics, metabolomics, RNA silencing, epigenetics, and other disciplines that may result in the emergence of new technologies and methods to better interpret causal relationships between microbiota and obesity.

Full Text Available Obesity, a global epidemic of the modern era, is a risk factor for cardiovascular diseases (CVD and diabetes. The pervasiveness of obesity and overweight in both developed as well as developing populations is on the rise and placing a huge burden on health and economic resources. Consequently, research to control this emerging epidemic is of utmost importance. Recently, host interactions with their resident gutmicrobiota (GM have been reported to be involved in the pathogenesis of many metabolic diseases, including obesity, diabetes, and CVD. Around 1014 microorganisms reside within the lower human intestine and many of these 1014microorganisms have developed mutualistic or commensal associations with the host and actively involved in many physiological processes of the host. However, dysbiosis (altered gut microbial composition with other predisposing genetic and environmental factors, may contribute to host metabolic disorders resulting in many ailments. Therefore, delineating the role of GM as a contributing factor to obesity is the main objective of this review.Obesity research, as a field is expanding rapidly due to major advances in nutrigenomics, metabolomics, RNA silencing, epigenetics and other disciplines that may result in the emergence of new technologies and methods to better interpret causal relationships between microbiota and obesity.

Obesity, a global epidemic of the modern era, is a risk factor for cardiovascular diseases (CVD) and diabetes. The pervasiveness of obesity and overweight in both developed as well as developing populations is on the rise and placing a huge burden on health and economic resources. Consequently, research to control this emerging epidemic is of utmost importance. Recently, host interactions with their resident gutmicrobiota (GM) have been reported to be involved in the pathogenesis of many metabolic diseases, including obesity, diabetes, and CVD. Around 1014 microorganisms reside within the lower human intestine and many of these 1014 microorganisms have developed mutualistic or commensal associations with the host and actively involved in many physiological processes of the host. However, dysbiosis (altered gut microbial composition) with other predisposing genetic and environmental factors, may contribute to host metabolic disorders resulting in many ailments. Therefore, delineating the role of GM as a contributing factor to obesity is the main objective of this review. Obesity research, as a field is expanding rapidly due to major advances in nutrigenomics, metabolomics, RNA silencing, epigenetics, and other disciplines that may result in the emergence of new technologies and methods to better interpret causal relationships between microbiota and obesity. PMID:27625997

It has become increasingly clear that the gutmicrobiota influences not only gastrointestinal physiology but also central nervous system (CNS) function by modulating signalling pathways of the microbiota-gut-brain axis. Understanding the neurobiological mechanisms underpinning the influence exerted by the gutmicrobiota on brain function and behaviour has become a key research priority. Microbial regulation of tryptophan metabolism has become a focal point in this regard, with dual emphasis on the regulation of serotonin synthesis and the control of kynurenine pathway metabolism. Here, we focus in detail on the latter pathway and begin by outlining the structural and functional dynamics of the gutmicrobiota and the signalling pathways of the brain-gut axis. We summarise preclinical and clinical investigations demonstrating that the gutmicrobiota influences CNS physiology, anxiety, depression, social behaviour, cognition and visceral pain. Pertinent studies are drawn from neurogastroenterology demonstrating the importance of tryptophan and its metabolites in CNS and gastrointestinal function. We outline how kynurenine pathway metabolism may be regulated by microbial control of neuroendocrine function and components of the immune system. Finally, preclinical evidence demonstrating direct and indirect mechanisms by which the gutmicrobiota can regulate tryptophan availability for kynurenine pathway metabolism, with downstream effects on CNS function, is reviewed. Targeting the gutmicrobiota represents a tractable target to modulate kynurenine pathway metabolism. Efforts to develop this approach will markedly increase our understanding of how the gutmicrobiota shapes brain and behaviour and provide new insights towards successful translation of microbiota-gut-brain axis research from bench to bedside. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'.

The gutmicrobiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gutmicrobiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gutmicrobiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gutmicrobiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gutmicrobiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gutmicrobiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics

Experimental analysis of gut microbial communities and their interactions with vertebrate hosts is conducted predominantly in domesticated animals that have been maintained in laboratory facilities for many generations. These animal models are useful for studying coevolved relationships between host and microbiota only if the microbial communities that occur in animals in lab facilities are representative of those that occur in nature. We performed 16S rRNA gene sequence-based comparisons of gut bacterial communities in zebrafish collected recently from their natural habitat and those reared for generations in lab facilities in different geographic locations. Patterns of gutmicrobiota structure in domesticated zebrafish varied across different lab facilities in correlation with historical connections between those facilities. However, gutmicrobiota membership in domesticated and recently caught zebrafish was strikingly similar, with a shared core gutmicrobiota. The zebrafish intestinal habitat therefore selects for specific bacterial taxa despite radical differences in host provenance and domestication status. PMID:21472014

The human gutmicrobiota is a complex community that provides important metabolic functions to the host. Consequently, alterations in the gutmicrobiota have been associated with the pathogenesis of several human diseases associated with a disturbance in metabolism, particularly those that have been increasing in incidence over the last several decades including obesity, diabetes and atherosclerosis. In this review, we explore how advances in deep DNA sequencing technology have provided us a greater understanding of the factors that influence that composition of the gutmicrobiota and its possible links to the pathogenesis of these diseases.

The gutmicrobiota has been linked with chronic diseases such as obesity in humans. However, the demonstration of causality between constituents of the microbiota and specific diseases remains an important challenge in the field. In this Opinion article, using Koch's postulates as a conceptual framework, I explore the chain of causation from alterations in the gutmicrobiota, particularly of the endotoxin-producing members, to the development of obesity in both rodents and humans. I then propose a strategy for identifying the causative agents of obesity in the human microbiota through a combination of microbiome-wide association studies, mechanistic analysis of host responses and the reproduction of diseases in gnotobiotic animals.

Functional gastrointestinal disorders (FGIDs) are highly prevalent and pose a significant burden on health care and society, and impact patients’ quality of life. FGIDs comprise a heterogeneous group of disorders, with unclear underlying pathophysiology. They are considered to result from the interaction of altered gut physiology and psychological factors via the gut-brain axis, where brain and gut symptoms are reciprocally influencing each other’s expression. Intestinal microbiota, as a part of the gut-brain axis, plays a central role in FGIDs. Patients with Irritable Bowel Syndrome, a prototype of FGIDs, display altered composition of the gutmicrobiota compared with healthy controls and benefit, at the gastrointestinal and psychological levels, from the use of probiotics and antibiotics. This review aims to recapitulate the available literature on FGIDs and microbiota-gut-brain axis. PMID:24921926

Functional gastrointestinal disorders (FGIDs) are highly prevalent and pose a significant burden on health care and society, and impact patients' quality of life. FGIDs comprise a heterogeneous group of disorders, with unclear underlying pathophysiology. They are considered to result from the interaction of altered gut physiology and psychological factors via the gut-brain axis, where brain and gut symptoms are reciprocally influencing each other's expression. Intestinal microbiota, as a part of the gut-brain axis, plays a central role in FGIDs. Patients with Irritable Bowel Syndrome, a prototype of FGIDs, display altered composition of the gutmicrobiota compared with healthy controls and benefit, at the gastrointestinal and psychological levels, from the use of probiotics and antibiotics. This review aims to recapitulate the available literature on FGIDs and microbiota-gut-brain axis.

Full Text Available Earthworms are the most ancient invertebrate animals on earth which can be used as a good source of pharmaceutical compounds. A study was carried out to find out the distribution of microorganisms in the gut of earthworm, Eudrilus eugeniae. Significant number of microbial populations in the gut of earthworm was observed and it was gradually increased from the initial day to final day of composting. Pigmented colonies of bacteria from earthwormgut were selectively isolated, the pigment was extracted from the culture broth and a presumptive test was carried out for the confirmation of prodigiosin. The pigment component was separated using thin layer chromatography and the structural elucidation of the compound was performed using U.V. spectroscopy. The inhibitory effect of prodigiosin on bacterial pathogens was studied and the results confirmed the antibacterial activity against gram positive bacteria. The anticancer activity of the prodigiosin pigment was evaluated under in vitro conditions against the breast cancer cell lines and it was observed that prodigiosin induced the apoptosis in MCF-7 cell lines in a dose dependent manner. Then the potential isolate was subjected to morphological and biochemical analysis and it was confirmed that the colonies were of Serratia marcescens. The results obtained from the present study indicated that earthwormgut is promising and could be a vital source of habitat possessing antimicrobial and anticancer activity.

Full Text Available The human gutmicrobiota is considered one of the most fascinating reservoirs of microbial diversity hosting between 400 to 1000 bacterial species distributed among nine phyla with Firmicutes, Bacteroidetes and Actinobacteria representing around 75% of the diversity. One of the most intriguing issues relates to understanding which microbial groups are active players in the maintenance of the microbiota homeostasis.Here, we describe the diversity of active microbial fractions compared with the whole community from raw human fecal samples. We studied four healthy volunteers by 16S rDNA gene pyrosequencing. The fractions were obtained by cell sorting based on bacterial RNA concentration. Bacterial families were observed to appear or disappear on applying a cell sorting method in which flow cytometry was used to evaluate the active cells by pyronin-Y staining of RNA. This method was able to detect active bacteria, indicating that the active players differed from that observed in raw fecal material. Generally, observations showed that in the active fractions, the number of reads related to Bacteroidetes decreased whereas several families from Clostridiales (Firmicutes were more highly represented. Moreover, a huge number of families appeared as part of the active fraction when cell sorting was applied, indicating reads that are simply statistically hidden by the total reads.

Intestinal tracts are among the most densely populated microbial ecosystems. Gutmicrobiota and their influence on the host have been well characterized in terrestrial vertebrates but much less so in fish. This is especially true for coral reef fishes, which are among the most abundant groups of vertebrates on earth. Surgeonfishes (family: Acanthuridae) are part of a large and diverse family of reef fish that display a wide range of feeding behaviours, which in turn has a strong impact on the reef ecology. Here, we studied the composition of the gutmicrobiota of nine surgeonfish and three nonsurgeonfish species from the Red Sea. High-throughput pyrosequencing results showed that members of the phylum Firmicutes, especially of the genus Epulopiscium, were dominant in the gutmicrobiota of seven surgeonfishes. Even so, there were large inter- and intraspecies differences in the diversity of surgeonfish microbiota. Replicates of the same host species shared only a small number of operational taxonomic units (OTUs), although these accounted for most of the sequences. There was a statistically significant correlation between the phylogeny of the host and their gutmicrobiota, but the two were not completely congruent. Notably, the gutmicrobiota of three nonsurgeonfish species clustered with some surgeonfish species. The microbiota of the macro- and microalgavores was distinct, while the microbiota of the others (carnivores, omnivores and detritivores) seemed to be transient and dynamic. Despite some anomalies, both host phylogeny and diet were important drivers for the intestinal microbial community structure of surgeonfishes from the Red Sea.

The intestinal tract is inhabited by a large diverse community of bacteria collectively referred to as the gutmicrobiota. Alterations in gutmicrobiota composition are associated with a variety of disease states including obesity, diabetes, and inflammatory bowel disease (IBD). Transplant of microbiota from diseased persons (or mice) to germfree mice transfers some aspects of disease phenotype, indicating that altered microbiota plays a role in disease establishment and manifestation. There are myriad potential mechanisms by which alterations in gutmicrobiota might promote disease, including increasing energy harvest, production of toxic metabolites, and molecular mimicry of host proteins. However, our research indicates that an overarching mechanism by which an aberrant microbiota negatively impacts health is by driving chronic inflammation. More specifically, we hypothesize that the histopathologically evident gut inflammation that defines IBD is a severe but relatively rare outcome of an altered host-microbiota relationship, while a much more common consequence of such disturbances is "low-grade" inflammation characterized by elevated proinflammatory gene expression that associates with, and may promote, metabolic syndrome. In this context, a variety of chronic inflammatory diseases may stem from inability of the mucosal immune system to properly manage a stable healthy relationship with the gutmicrobiota. While one's ability to manage their gutmicrobiota is dictated in part by genetics, it can be markedly influenced by the composition of the microbiota one inherits from their early environment. Moreover, the host-microbiota relationship can be perturbed by instigator bacteria or dietary components, which may prove to play a role in promoting chronic inflammatory disease states.

The gutmicrobiota of fish larvae evolves fast towards a complex community. Both host and environment affect the development of the gutmicrobiota; however, the relative importance of both is poorly understood. Determining specific changes in gut microbial populations in response to a change in an environmental factor is very complicated. Interactions between factors are difficult to separate and any response could be masked due to high inter-individual variation even for individuals that share a common environment. In this study we characterized and quantified the spatio-temporal variation in the gutmicrobiota of tilapia larvae, reared in recirculating aquaculture systems (RAS) or active suspension tanks (AS). Our results showed that variation in gutmicrobiota between replicate tanks was not significantly higher than within tank variation, suggesting that there is no tank effect on water and gutmicrobiota. However, when individuals were reared in replicate RAS, gutmicrobiota differed significantly. The highest variation was observed between individuals reared in different types of system (RAS vs. AS). Our data suggest that under experimental conditions in which the roles of deterministic and stochastic factors have not been precisely determined, compositional replication of the microbial communities of an ecosystem is not predictable. PMID:25072852

The gutmicrobiota of fish larvae evolves fast towards a complex community. Both host and environment affect the development of the gutmicrobiota; however, the relative importance of both is poorly understood. Determining specific changes in gut microbial populations in response to a change in an environmental factor is very complicated. Interactions between factors are difficult to separate and any response could be masked due to high inter-individual variation even for individuals that share a common environment. In this study we characterized and quantified the spatio-temporal variation in the gutmicrobiota of tilapia larvae, reared in recirculating aquaculture systems (RAS) or active suspension tanks (AS). Our results showed that variation in gutmicrobiota between replicate tanks was not significantly higher than within tank variation, suggesting that there is no tank effect on water and gutmicrobiota. However, when individuals were reared in replicate RAS, gutmicrobiota differed significantly. The highest variation was observed between individuals reared in different types of system (RAS vs. AS). Our data suggest that under experimental conditions in which the roles of deterministic and stochastic factors have not been precisely determined, compositional replication of the microbial communities of an ecosystem is not predictable.

The gut microbiome is known to be extensively involved in human health and disease. In order to reveal the metabolic relationship between host and microbiome, we monitored recovery of the gutmicrobiota composition and fecal profiles of mice after gentamicin and/or ceftriaxone treatments. This was performed by employing (1)H nuclear magnetic resonance (NMR)-based metabonomics and denaturing gradient gel electrophoresis (DGGE) fingerprint of gutmicrobiota. The common features of fecal metabolites postantibiotic treatment include decreased levels of short chain fatty acids (SCFAs), amino acids and primary bile acids and increased oligosaccharides, d-pinitol, choline and secondary bile acids (deoxycholic acid). This suggests suppressed bacterial fermentation, protein degradation and enhanced gut microbial modification of bile acids. Barnesiella, Prevotella, and Alistipes levels were shown to decrease as a result of the antibiotic treatment, whereas levels of Bacteroides, Enterococcus and Erysipelotrichaceae incertae sedis, and Mycoplasma increased after gentamicin and ceftriaxone treatment. In addition, there was a strong correlation between fecal profiles and levels of Bacteroides, Barnesiella, Alistipes and Prevotella. The integration of metabonomics and gutmicrobiota profiling provides important information on the changes of gutmicrobiota and their impact on fecal profiles during the recovery after antibiotic treatment. The correlation between gutmicrobiota and fecal metabolites provides important information on the function of bacteria, which in turn could be important in optimizing therapeutic strategies, and developing potential microbiota-based disease preventions and therapeutic interventions.

Full Text Available BACKGROUND: Earthworms play a critical role in organic matter decomposition because of the interactions they establish with microorganisms. The ingestion, digestion, assimilation of organic material in the gut and then casting is the first step in earthworm-microorganism interactions. The current knowledge of these direct effects is still limited for epigeic earthworm species, mainly those living in man-made environments. Here we tested whether and to what extent the earthworm Eisenia andrei is capable of altering the microbiological properties of fresh organic matter through gut associated processes; and if these direct effects are related to the earthworm diet. METHODOLOGY: To address these questions we determined the microbial community structure (phospholipid fatty acid profiles and microbial activity (fluorescein diacetate hydrolysis in the earthworm casts derived from three types of animal manure (cow, horse and pig manure, which differed in microbial composition. PRINCIPAL FINDINGS: The passage of the organic material through the gut of E. andrei reduced the total microbial biomass irrespective of the type of manure, and resulted in a decrease in bacterial biomass in all the manures; whilst leaving the fungi unaffected in the egested materials. However, unlike the microbial biomass, no such reduction was detected in the total microbial activity of cast samples derived from the pig manure. Moreover, no differences were found between cast samples derived from the different types of manure with regards to microbial community structure, which provides strong evidence for a bottleneck effect of worm digestion on microbial populations of the original material consumed. CONCLUSIONS/SIGNIFICANCE: Our data reveal that earthwormgut is a major shaper of microbial communities, thereby favouring the existence of a reduced but more active microbial population in the egested materials, which is of great importance to understand how biotic interactions

Background Earthworms play a critical role in organic matter decomposition because of the interactions they establish with microorganisms. The ingestion, digestion, assimilation of organic material in the gut and then casting is the first step in earthworm-microorganism interactions. The current knowledge of these direct effects is still limited for epigeic earthworm species, mainly those living in man-made environments. Here we tested whether and to what extent the earthworm Eisenia andrei is capable of altering the microbiological properties of fresh organic matter through gut associated processes; and if these direct effects are related to the earthworm diet. Methodology To address these questions we determined the microbial community structure (phospholipid fatty acid profiles) and microbial activity (fluorescein diacetate hydrolysis) in the earthworm casts derived from three types of animal manure (cow, horse and pig manure), which differed in microbial composition. Principal Findings The passage of the organic material through the gut of E. andrei reduced the total microbial biomass irrespective of the type of manure, and resulted in a decrease in bacterial biomass in all the manures; whilst leaving the fungi unaffected in the egested materials. However, unlike the microbial biomass, no such reduction was detected in the total microbial activity of cast samples derived from the pig manure. Moreover, no differences were found between cast samples derived from the different types of manure with regards to microbial community structure, which provides strong evidence for a bottleneck effect of worm digestion on microbial populations of the original material consumed. Conclusions/Significance Our data reveal that earthwormgut is a major shaper of microbial communities, thereby favouring the existence of a reduced but more active microbial population in the egested materials, which is of great importance to understand how biotic interactions within the decomposer

.... In the present review, we will describe how changes in the gutmicrobiota composition and/or activity by dietary fibres with prebiotic properties, can modulate host gene expression and metabolism...

...) mice with a normal gutmicrobiota. This behavioral phenotype is associated with altered expression of genes known to be involved in second messenger pathways and synaptic long-term potentiation in brain regions implicated in motor...

The gutmicrobiota plays an important role for humans in both health and disease. It is therefore important to understand how and to what extent choice of diet may influence the microbial community and the effects this has on the host. The variation in the normal human gutmicrobiota may however...... impede the discovery of correlations between dietary changes and compositional shifts in the microbiota by masking such effects. Although specific functional food ingredients, such as prebiotics, are known to have measurable effects on e.g. abundance of bifidobacteria, it is nevertheless clear...... that induced shifts in gutmicrobiota show large inter-individual variations. It thus seems plausible that knowing the microbiota composition could facilitate predictions as to how the community will react to dietary interventions thus moving towards some degree of personalised dietary recommendations. During...

Recent findings have demonstrated that the gut microbiome complements our human genome with at least 100-fold more genes. In contrast to our Homo sapiens-derived genes, the microbiome is much more plastic, and its composition changes with age and diet, among other factors. An altered gutmicrobiota has been associated with several diseases, including obesity and diabetes, but the mechanisms involved remain elusive. Here we discuss factors that affect the gut microbiome, how the gut microbiome may contribute to metabolic diseases, and how to study the gut microbiome. Next-generation sequencing and development of software packages have led to the development of large-scale sequencing efforts to catalog the human microbiome. Furthermore, the use of genetically engineered gnotobiotic mouse models may increase our understanding of mechanisms by which the gut microbiome modulates host metabolism. A combination of classical microbiology, sequencing, and animal experiments may provide further insights into how the gutmicrobiota affect host metabolism and physiology.

The vertebrate gutmicrobiota evolved in an environment typified by periodic fluctuations in nutrient availability, yet little is known about its responses to host feeding and fasting. Because many model species (e.g., mice) are adapted to lifestyles of frequent small meals, we turned to the Burmese python, a sit-and-wait foraging snake that consumes large prey at long intervals (>1 month), to examine the effects of a dynamic nutrient milieu on the gutmicrobiota. We employed multiplexed 16S ...

This review summarizes recent studies examining whole grain consumption and its effect on gutmicrobiota and satiety in healthy humans. Studies comparing whole grains to their refined grain counterparts were considered, as were studies comparing different grain types. Possible mechanisms linking microbial metabolism and satiety are described. Clinical trials show that whole grain wheat, maize, and barley alter the human gutmicrobiota, but these findings are based on a few studies that do not...

Full Text Available Colonization of gutmicrobiota in mammals during the early life is vital to host health. The miniature piglet has recently been considered as an optimal infant model. However, less is known about the development of gutmicrobiota in miniature piglets. Here, this study was conducted to explore how the gutmicrobiota develops in weaned Congjiang miniature piglets. In contrast to the relatively stabilized gut fungal community, gut bacterial community showed a marked drop in alpha diversity, accompanied by significant alterations in taxonomic compositions. The relative abundances of 24 bacterial genera significantly declined, whereas the relative abundances of 7 bacterial genera (Fibrobacter, Collinsella, Roseburia, Prevotella, Dorea, Howardella, and Blautia significantly increased with the age of weaned piglets. Fungal taxonomic analysis showed that the relative abundances of 2 genera (Kazachstania and Aureobasidium significantly decreased, whereas the relative abundances of 4 genera (Aspergillus, Cladosporium, Simplicillium, and Candida significantly increased as the piglets aged. Kazachstania telluris was the signature species predominated in gut fungal communities of weaned miniature piglets. The functional maturation of the gut bacterial community was characterized by the significantly increased digestive system, glycan biosynthesis and metabolism, and vitamin B biosynthesis as the piglets aged. These findings suggest that marked gut microbial changes in Congjiang miniature piglets may contribute to understand the potential gutmicrobiota development of weaned infants.

In the past century, noncommunicable diseases have surpassed infectious diseases as the principal cause of sickness and death, worldwide. Trillions of commensal microbes live in and on our body, and constitute the human microbiome. The vast majority of these microorganisms are maternally derived and live in the gut, where they perform functions essential to our health and survival, including: digesting food, activating certain drugs, producing short-chain fatty acids (which help to modulate gene expression by inhibiting the deacetylation of histone proteins), generating anti-inflammatory substances, and playing a fundamental role in the induction, training, and function of our immune system. Among the many roles the microbiome ultimately plays, it mitigates against untoward effects from our exposure to the environment by forming a biotic shield between us and the outside world. The importance of physical activity coupled with a balanced and healthy diet in the maintenance of our well-being has been recognized since antiquity. However, it is only recently that characterization of the host-microbiome intermetabolic and crosstalk pathways has come to the forefront in studying therapeutic design. As reviewed in this report, synthetic biology shows potential in developing microorganisms for correcting pathogenic dysbiosis (gutmicrobiota-host maladaptation), although this has yet to be proven. However, the development and use of small molecule drugs have a long and successful history in the clinic, with small molecule histone deacetylase inhibitors representing one relevant example already approved to treat cancer and other disorders. Moreover, preclinical research suggests that epigenetic treatment of neurological conditions holds significant promise. With the mouth being an extension of the digestive tract, it presents a readily accessible diagnostic site for the early detection of potential unhealthy pathogens resident in the gut. Taken together, the data outlined

The microorganisms living in our gut have been a black box to us for a long time. However, with the recent advances in high throughput DNA sequencing technologies, it is now possible to assess virtually all microorganisms in our gut including non-culturable ones. With the use of powerful bioinformatics tools to deal with multivariate analyses of huge amounts of data from metagenomics, metatranscriptomics, metabolomics, we now start to gain some important insights into these tiny gut inhabitants. Our knowledge is increasing about who they are, to some extent, what they do and how they affect our health. Gutmicrobiota have a broad spectrum of possible effects on health, from preventing serious diseases, improving immune system and gut health to stimulating the brain centers responsible for appetite and food intake control. Further, we may be on the verge of being capable of manipulating the gutmicrobiota by diet control to possibly improve our health. Diets consisting of different components that are fermentable by microbiota are substrates for different kinds of microbes in the gut. Thus, diet control can be used to favor the growth of some selected gut inhabitants. Nowadays, the gutmicrobiota is taken into account as a separate organ in human body and their activities and metabolites in gut have many physiological and neurological effects. In this mini-review, we discuss the diversity of gutmicrobiota, the technologies used to assess them, factors that affect microbial composition and metabolites that affect human physiology, and their potential applications in satiety control via the gut-brain axis.

Full Text Available As a barrier, gut commensal microbiota can protect against potential pathogenic microbes in the gastrointestinal tract. Crosstalk between gut microbes and immune cells promotes human intestinal homeostasis. Dysbiosis of gutmicrobiota has been implicated in the development of many human metabolic disorders like obesity, hepatic steatohepatitis, and insulin resistance in type 2 diabetes (T2D. Certain microbes, such as butyrate-producing bacteria, are lower in T2D patients. The transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome, but the exact pathogenesis remains unclear. H. pylori in the human stomach cause chronic gastritis, peptic ulcers, and gastric cancers. H. pylori infection also induces insulin resistance and has been defined as a predisposing factor to T2D development. Gastric and fecal microbiota may have been changed in H. pylori-infected persons and mice to promote gastric inflammation and specific diseases. However, the interaction of H. pylori and gutmicrobiota in regulating host metabolism also remains unknown. Further studies aim to identify the H. pylori-microbiota-host metabolism axis and to test if H. pylori eradication or modification of gutmicrobiota can improve the control of human metabolic disorders.

Metformin is commonly used as the first line of medication for the treatment of metabolic syndromes, such as obesity and type 2 diabetes (T2D). Recently, metformin-induced changes in the gutmicrobiota have been reported; however, the relationship between metformin treatment and the gutmicrobiota remains unclear. In this study, the composition of the gutmicrobiota was investigated using a mouse model of high-fat-diet (HFD)-induced obesity with and without metformin treatment. As expected, metformin treatment improved markers of metabolic disorders, including serum glucose levels, body weight, and total cholesterol levels. Moreover, Akkermansia muciniphila (12.44%±5.26%) and Clostridium cocleatum (0.10%±0.09%) abundances increased significantly after metformin treatment of mice on the HFD. The relative abundance of A. muciniphila in the fecal microbiota was also found to increase in brain heart infusion (BHI) medium supplemented with metformin in vitro. In addition to the changes in the microbiota associated with metformin treatment, when other influences were controlled for, a total of 18 KEGG metabolic pathways (including those for sphingolipid and fatty acid metabolism) were significantly upregulated in the gutmicrobiota during metformin treatment of mice on an HFD. Our results demonstrate that the gutmicrobiota and their metabolic pathways are influenced by metformin treatment.

Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy in women of reproductive age. It is difficult to treat PCOS because of its complex etiology and pathogenesis. Here, we characterized the roles of gutmicrobiota on the pathogenesis and treatments in letrozole (a nonsteroidal aromatase inhibitor) induced PCOS rat model. Changes in estrous cycles, hormonal levels, ovarian morphology and gutmicrobiota by PCR-DGGE and real-time PCR were determined. The results showed that PCOS rats displayed abnormal estrous cycles with increasing androgen biosynthesis and exhibited multiple large cysts with diminished granulosa layers in ovarian tissues. Meanwhile, the composition of gutmicrobiota in letrozole-treated rats was different from that in the controls. Lactobacillus, Ruminococcus and Clostridium were lower while Prevotella was higher in PCOS rats when compared with control rats. After treating PCOS rats with Lactobacillus and fecal microbiota transplantation (FMT) from healthy rats, it was found that the estrous cycles were improved in all 8 rats in FMT group, and in 6 of the 8 rats in Lactobacillus transplantation group with decreasing androgen biosynthesis. Their ovarian morphologies normalized. The composition of gutmicrobiota restored in both FMT and Lactobacillus treated groups with increasing of Lactobacillus and Clostridium, and decreasing of Prevotella. These results indicated that dysbiosis of gutmicrobiota was associated with the pathogenesis of PCOS. Microbiota interventions through FMT and Lactobacillus transplantation were beneficial for the treatments of PCOS rats.

Full Text Available Our immune system has evolved to recognize and eradicate pathogenic microbes. However, we have a symbiotic relationship with multiple species of bacteria that occupy the gut and comprise the natural commensal flora or microbiota. The microbiota is critically important for the breakdown of nutrients, and also assists in preventing colonization by potentially pathogenic bacteria. In addition, the gut commensal bacteria appears to be critical for the development of an optimally functioning immune system. Various studies have shown that individual species of the microbiota can induce very different types of immune cells (e.g., Th17 cells, Foxp3+ regulatory T cells and responses, suggesting that the composition of the microbiota can have an important influence on the immune response. Although the microbiota resides in the gut, it appears to have a significant impact on the systemic immune response. Indeed, specific gut commensal bacteria have been shown to affect disease development in organs other than the gut, and depending on the species, have been found to have a wide range of effects on diseases from induction and exacerbation to inhibition and protection. In this review, we will focus on the role that the gutmicrobiota plays in the development and progression of inflammatory/autoimmune disease, and we will also touch upon its role in allergy and cancer.

The microbiota of the human gut is gaining broad attention owing to its association with a wide range of diseases, ranging from metabolic disorders (e.g. obesity and type 2 diabetes) to autoimmune diseases (such as inflammatory bowel disease and type 1 diabetes), cancer and even neurodevelopmental disorders (e.g. autism). Having been increasingly used in biomedical research, mice have become the model of choice for most studies in this emerging field. Mouse models allow perturbations in gutmicrobiota to be studied in a controlled experimental setup, and thus help in assessing causality of the complex host-microbiota interactions and in developing mechanistic hypotheses. However, pitfalls should be considered when translating gut microbiome research results from mouse models to humans. In this Special Article, we discuss the intrinsic similarities and differences that exist between the two systems, and compare the human and murine core gutmicrobiota based on a meta-analysis of currently available datasets. Finally, we discuss the external factors that influence the capability of mouse models to recapitulate the gutmicrobiota shifts associated with human diseases, and investigate which alternative model systems exist for gutmicrobiota research.

The microbial communities that reside in the human gut (microbiota) and their impact on human health and disease are nowadays one of the most exciting new areas of research. A well-balanced microbial intestinal colonization in early postnatal life is necessary for the development of appropriate innate and adaptive immune responses and to establish immune homeostasis later in life. Although the composition and functional characteristics of a 'healthy' gutmicrobiota remain to be elucidated, perturbations in the microbial colonization of an infant's gastrointestinal tract have been associated with an increased risk of short- and long-term immunologically mediated diseases. Emerging evidence suggests that gutmicrobiota biomodulators, such as probiotics, prebiotics, synbiotics, and postbiotics may support disease prevention in infants who tend to have a delayed and/or aberrant initial colonization with reduced microbiota diversity (delivery by caesarean section, premature delivery, and excessive use of perinatal antibiotics). Under these dysbiosis conditions probiotics could act as 'surrogate' colonizers to prevent immune-mediated diseases. This review focuses on the influence of delivery mode on the colonization of the infant gastro-intestinal tract. In particular, it examines the manipulation of the gutmicrobiota composition through the use of gutmicrobiota biomodulators, in the management of aberrant initial gut colonization and subsequent consequences for the health of the offspring.

Full Text Available Progress in the understanding of the pathophysiology of irritable bowel syndrome (IBS, once thought to be a purely psychosomatic disease, has advanced considerably and low-grade inflammation and changes in the gutmicrobiota now feature as potentially important. The human gut harbours a huge microbial ecosystem, which is equipped to perform a variety of functions such as digestion of food, metabolism of drugs, detoxification of toxic compounds, production of essential vitamins, prevention of attachment of pathogenic bacteria to the gut wall, and maintenance of homeostasis in the gastrointestinal tract. A subset of patients with IBS may have a quantitative increase in bacteria in the small bowel (small intestinal bacterial overgrowth. Qualitative changes in gutmicrobiota have also been associated with IBS. Targeting the gutmicrobiota using probiotics and antibiotics has emerged as a potentially effective approach to the treatment of this, hitherto enigmatic, functional bowel disorder. The gutmicrobiota in health, quantitative and qualitative microbiota changes, and therapeutic manipulations targeting the microbiota in patients with IBS are reviewed in this paper.

Full Text Available The microbiota of the human gut is gaining broad attention owing to its association with a wide range of diseases, ranging from metabolic disorders (e.g. obesity and type 2 diabetes to autoimmune diseases (such as inflammatory bowel disease and type 1 diabetes, cancer and even neurodevelopmental disorders (e.g. autism. Having been increasingly used in biomedical research, mice have become the model of choice for most studies in this emerging field. Mouse models allow perturbations in gutmicrobiota to be studied in a controlled experimental setup, and thus help in assessing causality of the complex host-microbiota interactions and in developing mechanistic hypotheses. However, pitfalls should be considered when translating gut microbiome research results from mouse models to humans. In this Special Article, we discuss the intrinsic similarities and differences that exist between the two systems, and compare the human and murine core gutmicrobiota based on a meta-analysis of currently available datasets. Finally, we discuss the external factors that influence the capability of mouse models to recapitulate the gutmicrobiota shifts associated with human diseases, and investigate which alternative model systems exist for gutmicrobiota research.

Maturation and function of the immune system is highly influenced by the establishment of the microbiota in the gut, which in turn, particularly in infancy, is influenced by factors such as maternal microbiota and the environment, including diet. Studies have shown that although lymph nodes...

ABSTRACT There is growing evidence that individuals with colonic adenomas and carcinomas harbor a distinct microbiota. Alterations to the gutmicrobiota may allow the outgrowth of bacterial populations that induce genomic mutations or exacerbate tumor-promoting inflammation. In addition, it is likely that the loss of key bacterial populations may result in the loss of protective functions that are normally provided by the microbiota. We explored the role of the gutmicrobiota in colon tumorigenesis by using an inflammation-based murine model. We observed that perturbing the microbiota with different combinations of antibiotics reduced the number of tumors at the end of the model. Using the random forest machine learning algorithm, we successfully modeled the number of tumors that developed over the course of the model on the basis of the initial composition of the microbiota. The timing of antibiotic treatment was an important determinant of tumor outcome, as colon tumorigenesis was arrested by the use of antibiotics during the early inflammation period of the murine model. Together, these results indicate that it is possible to predict colon tumorigenesis on the basis of the composition of the microbiota and that altering the gutmicrobiota can alter the course of tumorigenesis. IMPORTANCE Mounting evidence indicates that alterations to the gutmicrobiota, the complex community of bacteria that inhabits the gastrointestinal tract, are strongly associated with the development of colorectal cancer. We used antibiotic perturbations to a murine model of inflammation-driven colon cancer to generate eight starting communities that resulted in various severities of tumorigenesis. Furthermore, we were able to quantitatively predict the final number of tumors on the basis of the initial composition of the gutmicrobiota. These results further bolster the evidence that the gutmicrobiota is involved in mediating the development of colorectal cancer. As a final proof of

Full Text Available Gutmicrobiota is essential to human health, playing a major and important role in the bidirectional communication between the gut and the brain. There is significant evidence linking gutmicrobiota and metabolic disorders such as obesity, diabetes and neuropsychiatric disorders such as schizophrenia, autism, anxiety, depression. New studies show microbiota can activate immune system, neural pathways and central nervous system signaling systems, including commensal, probiotic and pathogenic microorganisms in the gastrointestinal tract. This microorganisms are capable of producing and delivering neuroactive substances such as gamma-aminobutyric acid and serotonin, which act on the gut-brain axis. Preclinical evaluation in rodents suggests that certain probiotics possess antidepressant or anxiolytic activity. Effects may be mediated via the vagus nerve, spinal cord, immune system or neuroendocrine systems. Here we review recent literature that examines the impact of gutmicrobiota on the brain, behavior and psychiatric disorders.

The review highlights the role of metabolomics in studying human gut microbial metabolism. Microbial communities in our gut exert a multitude of functions with huge impact on human health and disease. Within the meta-omics discipline, gut microbiome is studied by (meta)genomics, (meta)transcriptomics, (meta)proteomics and metabolomics. The goal of metabolomics research applied to fecal samples is to perform their metabolic profiling, to quantify compounds and classes of interest, to characterize small molecules produced by gut microbes. Nuclear magnetic resonance spectroscopy and mass spectrometry are main technologies that are applied in fecal metabolomics. Metabolomics studies have been increasingly used in gutmicrobiota related research regarding health and disease with main focus on understanding inflammatory bowel diseases. The elucidated metabolites in this field are summarized in this review. We also addressed the main challenges of metabolomics in current and future gutmicrobiota research. The first challenge reflects the need of adequate analytical tools and pipelines, including sample handling, selection of appropriate equipment, and statistical evaluation to enable meaningful biological interpretation. The second challenge is related to the choice of the right animal model for studies on gutmicrobiota. We exemplified this using NMR spectroscopy for the investigation of cross-species comparison of fecal metabolite profiles. Finally, we present the problem of variability of human gutmicrobiota and metabolome that has important consequences on the concepts of personalized nutrition and medicine.

Parkinson's disease (PD) is characterized by alpha-synucleinopathy that affects all levels of the brain-gut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that the brain-gut axis interactions are significantly modulated by the gutmicrobiota via immunological, neuroendocrine, and direct neural mechanisms. Dysregulation of the brain-gut-microbiota axis in PD may be associated with gastrointestinal manifestations frequently preceding motor symptoms, as well as with the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain. Excessive stimulation of the innate immune system resulting from gut dysbiosis and/or small intestinal bacterial overgrowth and increased intestinal permeability may induce systemic inflammation, while activation of enteric neurons and enteric glial cells may contribute to the initiation of alpha-synuclein misfolding. Additionally, the adaptive immune system may be disturbed by bacterial proteins cross-reacting with human antigens. A better understanding of the brain-gut-microbiota axis interactions should bring a new insight in the pathophysiology of PD and permit an earlier diagnosis with a focus on peripheral biomarkers within the enteric nervous system. Novel therapeutic options aimed at modifying the gutmicrobiota composition and enhancing the intestinal epithelial barrier integrity in PD patients could influence the initial step of the following cascade of neurodegeneration in PD.

Full Text Available Background Accumulating evidence indicates interactions between human milk composition, particularly sugars (human milk oligosaccharides or HMO, the gutmicrobiota of human infants, and behavioral effects. Some HMO secreted in human milk are unable to be endogenously digested by the human infant but are able to be metabolized by certain species of gutmicrobiota, including Bifidobacterium longum subsp. infantis (B. infantis, a species sensitive to host stress (Bailey & Coe, 2004. Exposure to gut bacteria like B. infantisduring critical neurodevelopment windows in early life appears to have behavioral consequences; however, environmental, physical, and social stress during this period can also have behavioral and microbial consequences. While rodent models are a useful method for determining causal relationships between HMO, gutmicrobiota, and behavior, murine studies of gutmicrobiota usually employ oral gavage, a technique stressful to the mouse. Our aim was to develop a less-invasive technique for HMO administration to remove the potential confound of gavage stress. Under the hypothesis that stress affects gutmicrobiota, particularly B. infantis, we predicted the pups receiving a prebiotic solution in a less-invasive manner would have the highest amount of Bifidobacteria in their gut. Methods This study was designed to test two methods, active and passive, of solution administration to mice and the effects on their gut microbiome. Neonatal C57BL/6J mice housed in a specific-pathogen free facility received increasing doses of fructooligosaccharide (FOS solution or deionized, distilled water. Gastrointestinal (GI tracts were collected from five dams, six sires, and 41 pups over four time points. Seven fecal pellets from unhandled pups and two pellets from unhandled dams were also collected. Qualitative real-time polymerase chain reaction (qRT-PCR was used to quantify and compare the amount of Bifidobacterium, Bacteroides, Bacteroidetes, and

Background Accumulating evidence indicates interactions between human milk composition, particularly sugars (human milk oligosaccharides or HMO), the gutmicrobiota of human infants, and behavioral effects. Some HMO secreted in human milk are unable to be endogenously digested by the human infant but are able to be metabolized by certain species of gutmicrobiota, including Bifidobacterium longum subsp. infantis (B. infantis), a species sensitive to host stress (Bailey & Coe, 2004). Exposure to gut bacteria like B. infantisduring critical neurodevelopment windows in early life appears to have behavioral consequences; however, environmental, physical, and social stress during this period can also have behavioral and microbial consequences. While rodent models are a useful method for determining causal relationships between HMO, gutmicrobiota, and behavior, murine studies of gutmicrobiota usually employ oral gavage, a technique stressful to the mouse. Our aim was to develop a less-invasive technique for HMO administration to remove the potential confound of gavage stress. Under the hypothesis that stress affects gutmicrobiota, particularly B. infantis, we predicted the pups receiving a prebiotic solution in a less-invasive manner would have the highest amount of Bifidobacteria in their gut. Methods This study was designed to test two methods, active and passive, of solution administration to mice and the effects on their gut microbiome. Neonatal C57BL/6J mice housed in a specific-pathogen free facility received increasing doses of fructooligosaccharide (FOS) solution or deionized, distilled water. Gastrointestinal (GI) tracts were collected from five dams, six sires, and 41 pups over four time points. Seven fecal pellets from unhandled pups and two pellets from unhandled dams were also collected. Qualitative real-time polymerase chain reaction (qRT-PCR) was used to quantify and compare the amount of Bifidobacterium, Bacteroides, Bacteroidetes, and Firmicutes

Accumulating evidence indicates interactions between human milk composition, particularly sugars (human milk oligosaccharides or HMO), the gutmicrobiota of human infants, and behavioral effects. Some HMO secreted in human milk are unable to be endogenously digested by the human infant but are able to be metabolized by certain species of gutmicrobiota, including Bifidobacterium longum subsp. infantis (B. infantis), a species sensitive to host stress (Bailey & Coe, 2004). Exposure to gut bacteria like B. infantisduring critical neurodevelopment windows in early life appears to have behavioral consequences; however, environmental, physical, and social stress during this period can also have behavioral and microbial consequences. While rodent models are a useful method for determining causal relationships between HMO, gutmicrobiota, and behavior, murine studies of gutmicrobiota usually employ oral gavage, a technique stressful to the mouse. Our aim was to develop a less-invasive technique for HMO administration to remove the potential confound of gavage stress. Under the hypothesis that stress affects gutmicrobiota, particularly B. infantis, we predicted the pups receiving a prebiotic solution in a less-invasive manner would have the highest amount of Bifidobacteria in their gut. This study was designed to test two methods, active and passive, of solution administration to mice and the effects on their gut microbiome. Neonatal C57BL/6J mice housed in a specific-pathogen free facility received increasing doses of fructooligosaccharide (FOS) solution or deionized, distilled water. Gastrointestinal (GI) tracts were collected from five dams, six sires, and 41 pups over four time points. Seven fecal pellets from unhandled pups and two pellets from unhandled dams were also collected. Qualitative real-time polymerase chain reaction (qRT-PCR) was used to quantify and compare the amount of Bifidobacterium, Bacteroides, Bacteroidetes, and Firmicutes. Our results demonstrate

Irritable bowel syndrome (IBS) is a multifactorial functional disorder with no clearly defined etiology or pathophysiology. Modern culture-independent techniques have improved the understanding of the gut microbiota’s composition and demonstrated that an altered gutmicrobiota profile might be found in at least some subgroups of IBS patients. Research on IBS from a microbial perspective is gaining momentum and advancing. This review will therefore highlight potential links between the gut mic...

Quality control of laboratory animals has been mostly concentrated on eliminating and securing the absence of specific infections, but event barrier bred laboratory animals harbour a huge number of gut bacteria. There is scientific evidence that the nature of the gutmicrobiota especially in early...... correlated to factors related to early exposure to microorganisms, e.g. the so-called hygiene hypothesis claims that the increasing human incidence of allergy. T1D, RA and IBD may be due to the lack of such exposure. It is possible today by various molecular techniques to profile the gutmicrobiota...

The commensal microbiota impacts specific immune cell populations and their functions at peripheral sites, such as gut mucosal tissues. However, it remains unknown whether gutmicrobiota control immunity through regulation of hematopoiesis at primary immune sites. We reveal that germ-free mice display reduced proportions and differentiation potential of specific myeloid cell progenitors of both yolk sac and bone marrow origin. Homeostatic innate immune defects may lead to impaired early responses to pathogens. Indeed, following systemic infection with Listeria monocytogenes, germ-free and oral-antibiotic-treated mice display increased pathogen burden and acute death. Recolonization of germ-free mice with a complex microbiota restores defects in myelopoiesis and resistance to Listeria. These findings reveal that gut bacteria direct innate immune cell development via promoting hematopoiesis, contributing to our appreciation of the deep evolutionary connection between mammals and their microbiota.

BACKGROUND: Childhood and adolescent obesity has reached epidemic proportions worldwide. The pathogenesis of obesity is complex and multifactorial, in which genetic and environmental contributions seem important. The gutmicrobiota is increasingly documented to be involved in the dysmetabolism...... associated with obesity. METHODS: We conducted a systematic search for literature available before October 2015 in the PubMed and Scopus databases, focusing on the interplay between the gutmicrobiota, childhood obesity, and metabolism. RESULTS: The review discusses the potential role of the bacterial...... component of the human gutmicrobiota in childhood and adolescent-onset obesity, with a special focus on the factors involved in the early development of the gut bacterial ecosystem, and how modulation of this microbial community might serve as a basis for new therapeutic strategies in combating childhood...

Obesity and type 2 diabetes are metabolic diseases that have reached epidemic proportions worldwide. Although their etiology is complex, both result from interplay between behaviour, environment and genetic factors. Within ambient determinants, human overall gut bacteria have been identified as a crucial mediator of obesity and its consequences. Gutmicrobiota plays a crucial role in gastro-intestinal mucosa permeability and regulates the fermentation and absorption of dietary polyssacharides, which may explain its importance in the regulation of fat accumulation and the resultant development of obesity-related diseases. The main objective of this review is to address the pathogenic association between gutmicrobiota and obesity and to explore related innovative therapeutic targets. New insights into the role of the small bowel and gutmicrobiota in diabetes and obesity may make possible the development of integrated strategies to prevent and treat these metabolic disorders.

Animal nutrition is profoundly influenced by the gutmicrobiota, but knowledge of the scope and core mechanisms of the underlying animal-microbiota interactions is fragmentary. To investigate the nutritional traits shaped by the gutmicrobiota of Drosophila, we determined the microbiota-dependent response of multiple metabolic and performance indices to systematically varied diet composition. Diet-dependent differences between Drosophila bearing its unmanipulated microbiota (conventional flies) and experimentally deprived of its microbiota (axenic flies) revealed evidence for: microbial sparing of dietary B vitamins, especially riboflavin, on low-yeast diets; microbial promotion of protein nutrition, particularly in females; and microbiota-mediated suppression of lipid/carbohydrate storage, especially on high sugar diets. The microbiota also sets the relationship between energy storage and body mass, indicative of microbial modulation of the host signaling networks that coordinate metabolism with body size. This analysis identifies the multiple impacts of the microbiota on the metabolism of Drosophila, and demonstrates that the significance of these different interactions varies with diet composition and host sex.

Full Text Available Background: The intestinal microbiota composition varies between healthy and diseased individuals for numerous diseases. Although any cause or effect relationship between the alterations in the gutmicrobiota and disease is not always clear, targeting the intestinal microbiota might offer new possibilities for prevention and/or treatment of disease. Objective: Here we review some examples of manipulating the intestinal microbiota by prebiotics, probiotics, and fecal microbial transplants. Results: Prebiotics are best known for their ability to increase the number of bifidobacteria. However, specific prebiotics could potentially also stimulate other species they can also stimulate other species associated with health, like Akkermansia muciniphila, Ruminococcus bromii, the Roseburia/Enterococcus rectale group, and Faecalibacterium prausnitzii. Probiotics have beneficial health effects for different diseases and digestive symptoms. These effects can be due to the direct effect of the probiotic bacterium or its products itself, as well as effects of the probiotic on the resident microbiota. Probiotics can influence the microbiota composition as well as the activity of the resident microbiota. Fecal microbial transplants are a drastic intervention in the gutmicrobiota, aiming for total replacement of one microbiota by another. With numerous successful studies related to antibiotic-associated diarrhea and Clostridium difficile infection, the potential of fecal microbial transplants to treat other diseases like inflammatory bowel disease, irritable bowel syndrome, and metabolic and cardiovascular disorders is under investigation. Conclusions: Improved knowledge on the specific role of gutmicrobiota in prevention and treatment of disease will help more targeted manipulation of the intestinal microbiota. Further studies are necessary to see the (long term effects for health of these interventions.

Obesity increases the risk of type 2 diabetes, cardiovascular diseases, and certain cancers, which are among the leading causes of death worldwide. Obesity and obesity-related metabolic diseases are characterized by specific alterations in the human gutmicrobiota. Experimental studies with gutmicrobiota transplantations in mice and in humans indicate that a specific gutmicrobiota composition can be the cause and not just the consequence of the obese state and metabolic disease, which suggests a potential for gutmicrobiota modulation in prevention and treatment of obesity-related metabolic diseases. In addition, dietary intervention studies have suggested that modulation of the gutmicrobiota can improve metabolic risk markers in humans, but a causal role of the gutmicrobiota in such studies has not yet been established. Here, we review and discuss the role of the gutmicrobiota in obesity-related metabolic diseases and the potential of dietary modulation of the gutmicrobiota in metabolic disease prevention and treatment.

The gutmicrobiota influences many aspects of host metabolism. We have previously shown that the presence of a gutmicrobiota remodels lipid composition. Here we investigated how interaction between gutmicrobiota and dietary lipids regulates lipid composition in the liver and plasma, and gene...... of most lipid classes differed between mice fed lard and fish oil. However, the gutmicrobiota also affected lipid composition. The gutmicrobiota increased hepatic levels of cholesterol and cholesteryl esters in mice fed lard, but not in mice fed fish oil. Serum levels of cholesterol and cholesteryl...... esters were not affected by the gutmicrobiota. Genes encoding enzymes involved in cholesterol biosynthesis were downregulated by the gutmicrobiota in mice fed lard and were expressed at a low level in mice fed fish oil independent of microbial status. In summary, we show that gutmicrobiota...

Obesity increases the risk of type 2 diabetes, cardiovascular diseases, and certain cancers, which are among the leading causes of death worldwide. Obesity and obesity-related metabolic diseases are characterized by specific alterations in the human gutmicrobiota. Experimental studies with gutmicrobiota transplantations in mice and in humans indicate that a specific gutmicrobiota composition can be the cause and not just the consequence of the obese state and metabolic disease, which suggests a potential for gutmicrobiota modulation in prevention and treatment of obesity-related metabolic diseases. In addition, dietary intervention studies have suggested that modulation of the gutmicrobiota can improve metabolic risk markers in humans, but a causal role of the gutmicrobiota in such studies has not yet been established. Here, we review and discuss the role of the gutmicrobiota in obesity-related metabolic diseases and the potential of dietary modulation of the gutmicrobiota in metabolic disease prevention and treatment. PMID:26773017

Inflammatory diseases in mouse models are under strong impact from the gutmicrobiota. Therefore increased interindividual gutmicrobiota similarity may be seen as a way to reduce group sizes in mouse experiments. The composition of the gutmicrobiota is to a high extent defined by genetics......, and it is known that selecting siblings as mothers even in inbred colonies may increase the gutmicrobiota similarity among the mice with 3-4%. We therefore hypothesized that selective breeding of mice aiming at a high similarity in the gutmicrobiota would increase the interindividual similarity of the gut...... microbiota. BALB/cCrl mice were, however, found to have a mean heterozygosity of only 0.8% in their genome, and selection of breeders with a high similarity in the gutmicrobiota for three generations did not change the overall gutmicrobiota similarity, which was 66% in the P generation and 66%, 64% and 63...

The human gut is populated by an array of bacterial species, which develop important metabolic and immune functions, with a marked effect on the nutritional and health status of the host. Dietary component also play beneficial roles beyond basic nutrition, leading to the development of the functional food concept and nutraceuticals. Prebiotics, polyunsaturated fatty acids (PUFAs) and phytochemicals are the most well characterized dietary bioactive compounds. The beneficial effects of prebiotics mainly relay on their influence on the gutmicrobiota composition and their ability to generate fermentation products (short-chain fatty acids) with diverse biological roles. PUFAs include the omega-3 and omega-6 fatty acids, whose balance may influence diverse aspects of immunity and metabolism. Moreover, interactions between PUFAs and components of the gutmicrobiota may also influence their biological roles. Phytochemicals are bioactive non-nutrient plant compounds, which have raised interest because of their potential effects as antioxidants, antiestrogenics, anti-inflammatory, immunomodulatory, and anticarcinogenics. However, the bioavailability and effects of polyphenols greatly depend on their transformation by components of the gutmicrobiota. Phytochemicals and their metabolic products may also inhibit pathogenic bacteria while stimulate the growth of beneficial bacteria, exerting prebiotic-like effects. Therefore, the intestinal microbiota is both a target for nutritional intervention and a factor influencing the biological activity of other food compounds acquired orally. This review focuses on the reciprocal interactions between the gutmicrobiota and functional food components, and the consequences of these interactions on human health. 2009 Elsevier Ltd. All rights reserved.

Excess weight and obesity are severe public health threats worldwide. Recent evidence demonstrates that gutmicrobiota dysbiosis contributes to obesity and its comorbidities. The body weight-reducing and energy balancing effects of melatonin have been reported in several studies, but to date, no investigations toward examining whether the beneficial effects of melatonin are associated with gutmicrobiota have been carried out. In this study, we show that melatonin reduces body weight, liver steatosis, and low-grade inflammation as well as improving insulin resistance in high fat diet (HFD)-fed mice. High-throughput pyrosequencing of the 16S rRNA demonstrated that melatonin treatment significantly changed the composition of the gutmicrobiota in mice fed an HFD. The richness and diversity of gutmicrobiota were notably decreased by melatonin. HFD feeding altered 69 operational taxonomic units (OTUs) compare with a normal chow diet (NCD) group, and melatonin supplementation reversed 14 OTUs to the same configuration than those present in the NCD group, thereby impacting various functions, in particular through its ability to decrease the Firmicutes-to-Bacteroidetes ratio and increase the abundance of mucin-degrading bacteria Akkermansia, which is associated with healthy mucosa. Taken together, our results suggest that melatonin may be used as a probiotic agent to reverse HFD-induced gutmicrobiota dysbiosis and help us to gain a better understanding of the mechanisms governing the various melatonin beneficial effects.

The global prevalence of Fe deficiency is high and a common corrective strategy is oral Fe supplementation, which may affect the commensal gutmicrobiota and gastrointestinal health. The aim of the present study was to investigate the impact of different dietary Fe concentrations on the gutmicrobiota and gut health of rats inoculated with human faecal microbiota. Rats (8 weeks old, n 40) were divided into five (n 8 each) groups and fed diets differing only in Fe concentration during an Fe-depletion period (12 weeks) and an Fe-repletion period (4 weeks) as follows: (1) Fe-sufficient diet throughout the study period; (2) Fe-sufficient diet followed by 70 mg Fe/kg diet; (3) Fe-depleted diet throughout the study period; (4) Fe-depleted diet followed by 35 mg Fe/kg diet; (5) Fe-depleted diet followed by 70 mg Fe/kg diet. Faecal and caecal samples were analysed for gutmicrobiota composition (quantitative PCR and pyrosequencing) and bacterial metabolites (HPLC), and intestinal tissue samples were investigated histologically. Fe depletion did not significantly alter dominant populations of the gutmicrobiota and did not induce Fe-deficiency anaemia in the studied rats. Provision of the 35 mg Fe/kg diet after feeding an Fe-deficient diet significantly increased the abundance of dominant bacterial groups such as Bacteroides spp. and Clostridium cluster IV members compared with that of an Fe-deficient diet. Fe supplementation increased gut microbial butyrate concentration 6-fold compared with Fe depletion and did not affect histological colitis scores. The present results suggest that Fe supplementation enhances the concentration of beneficial gutmicrobiota metabolites and thus may contribute to gut health.

Emerging evidence supports novel roles for vitamin K in cardiometabolic health, some of which may be unique to the bacterially synthesized vitamin K forms known as menaquinones. However, factors influencing menaquinone biosynthesis by the gutmicrobiota and associations with cardiometabolic health have not been examined. The objective of this study was to identify associations between fecal menaquinone profiles, gutmicrobiota composition, and biomarkers of cardiometabolic health. The menaquinone profile and gutmicrobiota structure were periodically measured in fecal samples collected from 77 overweight Chinese adults who consumed a prescribed diet previously shown to alter gutmicrobiota composition and to improve cardiometabolic biomarkers. Covariance among menaquinones within individual fecal samples partitioned individuals into 2 distinct groups, herein introduced as menaquinotypes of the human gut. Menaquinotypes were characterized by differences in menaquinone (MK) 5 and MK9-MK13 and differences in the relative abundance of several operational taxonomic units (OTUs) delineated at the species level, predominantly within the genera Prevotella spp. and Bacteroides spp. Fecal MK4, MK6, and MK8 decreased during the intervention (P 100 OTUs were associated with altered fecal content of ≥1 individual menaquinone. The strongest and most consistent relations were between Prevotella spp. and MK5 and MK11-MK13, between Bacteroides spp. and MK9 and MK10, and between Escherichia/Shigella spp. and MK8. Neither individual menaquinones nor menaquinotypes were longitudinally associated with markers of glycemia, insulin resistance, or inflammation. These findings suggest that variability in fecal menaquinone content is predominantly determined by relatively few genera within the gutmicrobiota and that diet-mediated alterations in gutmicrobiota composition may provide a feasible approach for altering gut menaquinone content. This trial was registered at the Chinese

Plasmodium infections result in clinical presentations that range from asymptomatic to severe malaria, resulting in ∼1 million deaths annually. Despite this toll on humanity, the factors that determine disease severity remain poorly understood. Here, we show that the gutmicrobiota of mice influences the pathogenesis of malaria. Genetically similar mice from different commercial vendors, which exhibited differences in their gut bacterial community, had significant differences in parasite burden and mortality after infection with multiple Plasmodium species. Germfree mice that received cecal content transplants from "resistant" or "susceptible" mice had low and high parasite burdens, respectively, demonstrating the gutmicrobiota shaped the severity of malaria. Among differences in the gut flora were increased abundances of Lactobacillus and Bifidobacterium in resistant mice. Susceptible mice treated with antibiotics followed by yogurt made from these bacterial genera displayed a decreased parasite burden. Consistent with differences in parasite burden, resistant mice exhibited an elevated humoral immune response compared with susceptible mice. Collectively, these results identify the composition of the gutmicrobiota as a previously unidentified risk factor for severe malaria and modulation of the gutmicrobiota (e.g., probiotics) as a potential treatment to decrease parasite burden.

Obesity is characterised by altered gutmicrobiota, low-grade inflammation and increased endocannabinoid (eCB) system tone; however, a clear connection between gutmicrobiota and eCB signalling has yet to be confirmed. Here, we report that gutmicrobiota modulate the intestinal eCB system tone, which in turn regulates gut permeability and plasma lipopolysaccharide (LPS) levels. The impact of the increased plasma LPS levels and eCB system tone found in obesity on adipose tissue metabolism (e.g. differentiation and lipogenesis) remains unknown. By interfering with the eCB system using CB(1) agonist and antagonist in lean and obese mouse models, we found that the eCB system controls gut permeability and adipogenesis. We also show that LPS acts as a master switch to control adipose tissue metabolism both in vivo and ex vivo by blocking cannabinoid-driven adipogenesis. These data indicate that gutmicrobiota determine adipose tissue physiology through LPS-eCB system regulatory loops and may have critical functions in adipose tissue plasticity during obesity.

Although hibernating mammals wake occasionally to eat during torpor, this period represents a state of fasting. Fasting is known to alter the gutmicrobiota in nonhibernating mammals; therefore, hibernation may also affect the gutmicrobiota. However, there are few reports of gutmicrobiota in hibernating mammals. The present study aimed to compare the gutmicrobiota in hibernating torpid Syrian hamsters with that in active counterparts by using culture-independent analyses. Hamsters were all...

Obesity develops from a prolonged imbalance of energy intake and energy expenditure. However, the relatively recent discovery that the composition and function of the gutmicrobiota impacts on obesity has lead to an explosion of interest in what is now a distinct research field. Here, research relating to the links between the gutmicrobiota, diet and obesity will be reviewed under five major headings: (1) the gutmicrobiota of lean and obese animals, (2) the composition of the gutmicrobiota...

Gutmicrobiota are intricately involved in the development of obesity-related metabolic diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes, and insulin resistance. In the current review, we discuss the role of gutmicrobiota in the development of NAFLD by focusing on the mechanisms of gutmicrobiota-mediated host energy metabolism, insulin resistance, regulation of bile acids and choline metabolism, as well as gutmicrobiota-targeted therapy. We also discuss the applic...

Gutmicrobiota have recently been a topic of great interest in the field of microbiology, particularly their role in normal physiology and its influence on human health in disease. A large body of research has supported the presence of a pathway of communication between the gut and the brain, modulated by gutmicrobiota, giving rise to the term “microbiota-gut-brain” axis. It is now thought that, through this pathway, microbiota can affect behaviour and modulate brain plasticity and cognitive...

The gutmicrobiota has major impact on the individual. Here we show that the gutmicrobiota influence behavior in the subchronic PCP induced animal model of schizophrenia. The gutmicrobiota were changed in the group treated subchronic with PCP, and restoration coincided with normalisation...

Composed of trillions of individual microbes, the human gutmicrobiota has adapted to the uniquely diverse environments found in the human intestine. Quickly responding to the variances in the ingested food, the microbiota interacts with the host via reciprocal biochemical signaling to coordinate the exchange of nutrients and proper immune function. Host and microbiota function as a unit which guards its balance against invasion by potential pathogens and which undergoes natural selection. Disturbance of the microbiota composition, or dysbiosis, is often associated with human disease, indicating that, while there seems to be no unique optimal composition of the gutmicrobiota, a balanced community is crucial for human health. Emerging knowledge of the ecology of the microbiota-host synergy will have an impact on how we implement antibiotic treatment in therapeutics and prophylaxis and how we will consider alternative strategies of global remodeling of the microbiota such as fecal transplants. Here we examine the microbiota-human host relationship from the perspective of the microbial community dynamics. PMID:28769880

Full Text Available Perinatal programming, a dominant theory for the origins of cardiovascular disease, proposes that environmental stimuli influence developmental pathways during critical periods of prenatal and postnatal development, inducing permanent changes in metabolism. In this paper, we present evidence for the perinatal programming of asthma via the intestinal microbiome. While epigenetic mechanisms continue to provide new explanations for the programming hypothesis of asthma development, it is increasingly apparent that the intestinal microbiota plays an independent and potentially interactive role. Commensal gut bacteria are essential to immune system development, and exposures disrupting the infant gutmicrobiota have been linked to asthma. This paper summarizes the recent findings that implicate caesarean delivery, breastfeeding, perinatal stress, probiotics, and antibiotics as modifiers of infant gutmicrobiota in the development of asthma.

Full Text Available Human beings harbor gut microbial communities that are essential to preserve human health. Molded by the human genome, the gutmicrobiota is an adaptive component of the human superorganisms that allows host adaptation at different timescales, optimizing host physiology from daily life to lifespan scales and human evolutionary history. The gutmicrobiota continuously changes from birth up to the most extreme limits of human life, reconfiguring its metagenomic layout in response to daily variations in diet or specific host physiological and immunological needs at different ages. On the other hand, the microbiota plasticity was strategic to face changes in lifestyle and dietary habits along the course of the recent evolutionary history, that has driven the passage from Paleolithic hunter-gathering societies to Neolithic agricultural farmers to modern Westernized societies.

The impact of flavonoids has been discussed on the relative viability of bacterial groups in human microbiota. This study was aimed to compare the modulation of various flavonoids, including quercetin, catechin and puerarin, on gutmicrobiota culture in vitro, and analyze the interactions between bacterial species using fructo-oligosaccharide (FOS) as carbon source under the stress of flavonoids. Three plant flavonoids, quercetin, catechin, and puerarin, were added into multispecies culture to ferment for 24 h, respectively. The bacterial 16S rDNA amplicons were sequenced, and the composition of microbiota community was analyzed. The results revealed that the tested flavonoids, quercetin, catechin, and puerarin, presented different activities of regulating gutmicrobiota; flavonoid aglycones, but not glycosides, may inhibit growth of certain species. Quercetin and catechin shaped unique biological webs. Bifidobacterium spp. was the center of the biological web constructed in this study.

Full Text Available Nonalcoholic fatty liver disease is the hepatic expression of metabolic syndrome, being frequently associated with obesity, insulin resistance, and dyslipidemia. Recent lines of evidence have demonstrated a role of gutmicrobiota in insulin resistance, obesity, and associated metabolic disturbances, raising the interest in its relationship with NAFLD pathogenesis. Therefore, intestinal microbiota has emerged as a potential factor involved in NAFLD, through different pathways, including its influence in energy storage, lipid and choline metabolism, ethanol production, immune balance, and inflammation. The main objective of this review is to address the pathogenic association of gutmicrobiota to NAFLD. This comprehension may allow the development of integrated strategies to modulate intestinal microbiota in order to treat NAFLD.

Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM) but incomplete restoration of healthy growth remains a major problem1,2. The relationships between the type of nutritional intervention, the gutmicrobiota, and therapeutic responses are unclear. In the current study, bacterial species whose proportional representation define a healthy gutmicrobiota as it assembles during the first two postnatal years were identified by applying a machine-learning-based approach to 16S rRNA datasets generated from monthly fecal samples obtained from a birth-cohort of children, living in an urban slum of Dhaka, Bangladesh, who exhibited consistently healthy growth. These age-discriminatory bacterial species were incorporated into a model that computes a ‘relative microbiota maturity index’ and ‘microbiota-for-age Z-score’ that compare development (defined here as maturation) of a child’s fecal microbiota relative to healthy children of similar chronologic age. The model was applied to twins and triplets (to test for associations of these indices with genetic and environmental factors including diarrhea), children with SAM enrolled in a randomized trial of two food interventions, and children with moderate acute malnutrition. Our results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions. Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements. Microbiota maturity indices provide a microbial measure of human postnatal development, a way of classifying malnourished states, and a parameter for judging therapeutic efficacy. More prolonged interventions with existing or new therapeutic foods and/or addition of gut microbes may be needed to achieve enduring repair of gutmicrobiota immaturity in childhood malnutrition and improve clinical outcomes. PMID

Cecal microbiota from type 2 diabetic (db/db) and control (db/(+)) mice was obtained following 6 weeks of sedentary or exercise activity. qPCR analysis revealed a main effect of exercise, with greater abundance of select Firmicutes species and lower Bacteroides/Prevotella spp. in both normal and diabetic exercised mice compared with sedentary counterparts. Conversely, Bifidobacterium spp. was greater in exercised normal but not diabetic mice (exercise × diabetes interaction). How exercise influences gutmicrobiota requires further investigation.

Type 1 diabetes is a T cell-mediated autoimmune disease. Environmental factors play an important role in the initiation of the disease in genetically predisposed individuals. With the improved control of infectious disease, the incidence of autoimmune diseases, particularly type 1 diabetes, has dramatically increased in developed countries. Increasing evidence suggests that gutmicrobiota are involved in the pathogenesis of type 1 diabetes. Here we focus on recent advances in this field and provide a rationale for novel therapeutic strategies targeting gutmicrobiota for the prevention of type 1 diabetes.

Many epidemiological and experimental studies have suggested that dietary fiber plays an important role in colon cancer prevention. These findings may relate to the ability of fiber to reduce the contact time of carcinogens within the intestinal lumen and to promote healthy gutmicrobiota, which modifies the host's metabolism in various ways. Elucidation of the mechanisms by which dietary fiber-dependent changes in gutmicrobiota enhance bile acid deconjugation, produce short chain fatty acids, and modulate inflammatory bioactive substances can lead to a better understanding of the beneficial role of dietary fiber. This article reviews the current knowledge concerning the mechanisms via which dietary fiber protects against colon cancer.

The distal gut harbours microbial communities that outnumber our own eukaryotic cells. The contribution of the gutmicrobiota to the development of several diseases (e.g. obesity, type 2 diabetes, steatosis, cardiovascular diseases and inflammatory bowel diseases) is becoming clear, although the causality remains to be proven in humans. Global changes in the gutmicrobiota have been observed by a number of culture-dependent and culture-independent methods, and while the latter have mostly included 16S ribosomal RNA gene analyses, more recent studies have utilized DNA sequencing of whole-microbial communities. Altogether, these high-throughput methods have facilitated the identification of novel candidate bacteria and, most importantly, metabolic functions that might be associated with obesity and type 2 diabetes. This review discusses the association between specific taxa and obesity, together with the techniques that are used to characterize the gutmicrobiota in the context of obesity and type 2 diabetes. Recent results are discussed in the framework of the interactions between gutmicrobiota and host metabolism.

Full Text Available AbstractThe microbiota that resides in the gastrointestinal tract provides essential health benefits to the host. In particular, they regulate immune homeostasis. Recently, several evidences indicate that alteration in the gut microbial community can cause infectious and non-infectious diseases. Tuberculosis (TB is the most devastating disease, inflicting mortality and morbidity. It remains unexplored, whether changes in the gutmicrobiota can provoke or prevent TB. In the current study, we have demonstrated the antibiotics driven changes in the gut microbial composition and their impact on the survival of Mtb in the lungs, liver and spleen of infected mice, compared to those with intact microbiota. Interestingly, dysbiosis of microbes showed significant increase in the bacterial burden in lungs and dissemination of Mtb to spleen and liver. Further, elevation in the number of Tregs and decline in the pool of IFN-γ and TNF-α releasing CD4 T cells was noticed. Interestingly, fecal transplantation in the gutmicrobiota disrupted animals exhibited improved Th1 immunity and lesser Tregs population. Importantly, these animals displayed reduced severity to Mtb infection. This study for the first time demonstrated the novel role of gut microbes in the susceptibility to TB and its prevention by microbial implants. In future, microbial therapies may help in treating patients suffering from TB.

Progress in the understanding of the pathophysiology of irritable bowel syndrome (IBS), once thought to be a purely psychosomatic disease, has advanced considerably and low-grade inflammation and changes in the gutmicrobiota now feature as potentially important. The human gut harbours a huge microbial ecosystem, which is equipped to perform a variety of functions such as digestion of food, metabolism of drugs, detoxification of toxic compounds, production of essential vitamins, prevention of...

Microbiota assembly is perturbed in children with undernutrition, resulting in persistent microbiota immaturity that is not rescued by current nutritional interventions. Evidence is accumulating that this immaturity is causally related to the pathogenesis of undernutrition and its lingering sequelae. Preclinical models in which human gut communities are replicated in gnotobiotic mice have provided an opportunity to identify and predict the effects of different dietary ingredients on microbiota structure, expressed functions, and host biology. This capacity sets the stage for proof-of-concept tests designed to deliberately shape the developmental trajectory and configurations of microbiota in children representing different geographies, cultural traditions, and states of health. Developing these capabilities for microbial stewardship is timely given the global health burden of childhood undernutrition, the effects of changing eating practices brought about by globalization, and the realization that affordable nutritious foods need to be developed to enhance our capacity to cultivate healthier microbiota in populations at risk for poor nutrition. PMID:25815983

The microbiome has an important role in human health. Changes in the microbiota can confer resistance to or promote infection by pathogenic bacteria. Antibiotics have a profound impact on the microbiota that alters the nutritional landscape of the gut and can lead to the expansion of pathogenic populations. Pathogenic bacteria exploit microbiota-derived sources of carbon and nitrogen as nutrients and regulatory signals to promote their own growth and virulence. By eliciting inflammation, these bacteria alter the intestinal environment and use unique systems for respiration and metal acquisition to drive their expansion. Unravelling the interactions between the microbiota, the host and pathogenic bacteria will produce strategies for manipulating the microbiota against infectious diseases.

There is a growing awareness of the potential for microbiota to influence gut-brain communication in health and disease. A variety of strategies have been used to study the impact of the microbiota on brain function and these include antibiotic use, probiotic treatments, fecal microbiota transplantation, gastrointestinal infection studies, and germ-free studies. All of these approaches provide evidence to support the view that the microbiota can influence brain chemistry and consequently behavior. Efforts are now turning to investigate the role of microbiota in animal models of psychopathology. Animal models of depression are thus essential in studying the complex interplay between the microbiota and brain. Recent studies published in this Journal and elsewhere demonstrate that there is a distinct perturbation of the composition of gutmicrobiota in animal models of depression and chronic stress. This has direct implications for the development of psychobiotic-based therapeutic strategies for psychiatric disorders. Moreover, given that affective co-morbidities, such as major depression and anxiety states, are common in patients presenting with irritable bowel syndrome (IBS), it may have implications for functional bowel disorders also. Further studies require appropriately phenotyped patients with depression and/or IBS using a judicious use of techniques including functional imaging and in depth microbial pyrosequencing.

The gutmicrobiota has major impact on the individual. Here we show that the gutmicrobiota influence behavior in the subchronic PCP induced animal model of schizophrenia. The gutmicrobiota were changed in the group treated subchronic with PCP, and restoration coincided with normalisation...... of memory performance in lister hooded rats. Furthermore the individual gutmicrobiota correlated to the individual behavior abserved in the tests conducted. In conclusion results show an influence of the gutmicrobiota on behavior in this model, and therefore it might be relavant to include the information...

Obesity increases the risk of type 2 diabetes, cardiovascular diseases, and certain cancers, which are among the leading causes of death worldwide. Obesity and obesity-related metabolic diseases are characterized by specific alterations in the human gutmicrobiota. Experimental studies with gut...... microbiota transplantations in mice and in humans indicate that a specific gutmicrobiota composition can be the cause and not just the consequence of the obese state and metabolic disease, which suggests a potential for gutmicrobiota modulation in prevention and treatment of obesity-related metabolic...... diseases. In addition, dietary intervention studies have suggested that modulation of the gutmicrobiota can improve metabolic risk markers in humans, but a causal role of the gutmicrobiota in such studies has not yet been established. Here, we review and discuss the role of the gutmicrobiota in obesity...

Many epidemiological and experimental studies have suggested that dietary fiber plays an important role in colon cancer prevention. These findings may relate to the ability of fiber to reduce the contact time of carcinogens within the intestinal lumen and to promote healthy gutmicrobiota, which mod...

The colonization and development of gutmicrobiota immediately after birth is highly variable and depends on several factors, such as delivery mode and modality of feeding during the first months of life. A cohort of 31 mother and neonate pairs, including 25 at-term caesarean (CS) and 6 vaginally (V

There is an emerging body of evidence linking the intestinal microbiota with autism spectrum disorders (ASD). Studies have demonstrated differences in the composition of gut bacteria between children with ASD and controls. Certain intestinal bacteria have been observed in abundance and may be involved in the pathogenesis of ASD; including members…

There is an emerging body of evidence linking the intestinal microbiota with autism spectrum disorders (ASD). Studies have demonstrated differences in the composition of gut bacteria between children with ASD and controls. Certain intestinal bacteria have been observed in abundance and may be involved in the pathogenesis of ASD; including members…

The realization that the microbiota-gut-brain axis plays a critical role in health and disease has emerged over the past decade. The brain-gut axis is a bidirectional communication system between the central nervous system (CNS) and the gastrointestinal tract. Regulation of the microbiota-brain-gut axis is essential for maintaining homeostasis, including that of the CNS. The routes of this communication are not fully elucidated but include neural, humoral, immune, and metabolic pathways. A number of approaches have been used to interrogate this axis including the use of germ-free animals, probiotic agents, antibiotics, or animals exposed to pathogenic bacterial infections. Together, it is clear that the gutmicrobiota can be a key regulator of mood, cognition, pain, and obesity. Understanding microbiota-brain interactions is an exciting area of research which may contribute new insights into individual variations in cognition, personality, mood, sleep, and eating behavior, and how they contribute to a range of neuropsychiatric diseases ranging from affective disorders to autism and schizophrenia. Finally, the concept of psychobiotics, bacterial-based interventions with mental health benefit, is also emerging.

The characterization of gutmicrobiota has become an important area of research in several clinical conditions, including type 2 diabetes (T2DM). Changes in the composition and/or metabolic activity of the gutmicrobiota can contribute to human health. Thus, this review discusses the effects of probiotics and gutmicrobiota on metabolic control in these individuals. Relevant studies were obtained from electronic databases such as PubMed/Medline and ISI Web of Science. The main probiotics used in these studies belonged to the genera Lactobacillus and Bifidobacterium. The authors found seven randomized placebo-controlled clinical trials and 13 experimental studies directly related to the effect of probiotics on metabolic control in the context of T2DM. The hypothesis that gutmicrobiota plays a role in the development of diabetes indicates an important beginning, and the potential of probiotics to prevent and reduce the severity of T2DM is better observed in animal studies. In clinical trials, the use of probiotics in glycemic control presented conflicting results, and only few studies have attempted to evaluate factors that justify metabolic changes, such as markers of oxidative stress, inflammation, and incretins. Thus, further research is needed to assess the effects of probiotics in the metabolism of diabetic individuals, as well as the main mechanisms involved in this complex relationship.

Full Text Available This review summarizes recent studies examining whole grain consumption and its effect on gutmicrobiota and satiety in healthy humans. Studies comparing whole grains to their refined grain counterparts were considered, as were studies comparing different grain types. Possible mechanisms linking microbial metabolism and satiety are described. Clinical trials show that whole grain wheat, maize, and barley alter the human gutmicrobiota, but these findings are based on a few studies that do not include satiety components, so no functional claims between microbiota and satiety can be made. Ten satiety trials were evaluated and provide evidence that whole oats, barley, and rye can increase satiety, whereas the evidence for whole wheat and maize is not compelling. There are many gaps in the literature; no one clinical trial has examined the effects of whole grains on satiety and gutmicrobiota together. Once understanding the impact of whole grains on satiety and microbiota is more developed, then particular grains might be used for better appetite control. With this information at hand, healthcare professionals could make individual dietary recommendations that promote satiety and contribute to weight control.

inoculation. The results demonstrate, that the donor gutmicrobiota was introduced, established, and changed the gutmicrobiota of the recipients. Six weeks after inoculation, the differences persisted, however alteration of the gutmicrobiota occurred with time within the groups. The clinical parameters...... to conventional antibiotic-treated mice was possible at least for a time period during which the microbiota may permanently modulate important host functions....

Full Text Available The human gastro-intestinal tract hosts a complex and diverse microbial community, whose collective genetic coding capacity vastly exceeds that of the human genome. As a consequence, the gutmicrobiota produces metabolites from a large range of molecules that host’s enzymes are not able to convert. Among these molecules, two main classes of steroids, cholesterol and bile acids, denote two different examples of bacterial metabolism in the gut. Therefore, cholesterol is mainly converted into coprostanol, a non absorbable sterol which is excreted in the feces. Moreover, this conversion occurs in a part of the human population only. Conversely, the primary bile acids (cholic and chenodeoxycholic acids are converted to over twenty different secondary bile acid metabolites by the gutmicrobiota. The main bile salt conversions, which appear in the gut of the whole human population, include deconjugation, oxidation and epimerization of hydroxyl groups at C3, C7 and C12, 7-dehydroxylation, esterification and desulfatation. If the metabolisms of cholesterol and bile acids by the gutmicrobiota are known for decades, their consequences on human health and disease are poorly understood and only start to be considered.

Full Text Available Antibiotics strongly disrupt the human gutmicrobiota, which in consequence loses its colonization resistance capacity, allowing infection by opportunistic pathogens such as Clostridium difficile. This bacterium is the main cause of antibiotic-associated diarrhea and a current problem in developed countries, since its incidence and severity have increased during the last years. Furthermore, the emergence of antibiotic resistance strains has reduced the efficiency of the standard treatment with antibiotics, leading to a higher rate of relapses. Here, we review recent efforts focused on the impact of antibiotics in the gut microbiome and their relationship with C. difficile colonization, as well as, in the identification of bacteria and mechanisms involved in the protection against C. difficile infection. Since a healthy gutmicrobiota is able to avoid pathogen colonization, restoration of the gutmicrobiota seems to be the most promising approach to face C. difficile infection, especially for recurrent cases. Therefore, it would be possible to design probiotics for patients undergoing antimicrobial therapies in order to prevent or fight the expansion of the pathogen in the gut ecosystem.

Diet is a major force that shapes the composition and activity of the gutmicrobiota. This is evident from alterations in gutmicrobiota composition after weaning or drastic dietary changes. Owing to the complexity of the microbiota, interactions of intestinal bacteria with the host are difficult to study. Gnotobiotic animal models offer the opportunity to reduce the complexity and the interindividual variability of the intestinal microbiota. Germ-free animals were associated with a simplified microbial community consisting of eight bacterial species, that are found in the human gut. These microbes were selected because their genome sequences are available, and they mimic to some extent the metabolic activity of the human gutmicrobiota. The microbiota responded to dietary modifications by changes in the relative proportions of the community members. This model offers the chance to better define the role of intestinal bacteria in obesity development, but little is known on how diet affects intestinal bacteria at the cellular level. Mice monoassociated with Escherichia coli were used as a simplified model to investigate the influence of dietary factors on bacterial protein expression in the intestine. The mice were fed three different diets: a carbohydrate (lactose)-rich diet, a protein-rich diet and a diet rich in starch. The lactose-rich diet led to an induction of proteins involved in E. coli's oxidative stress response (Fur, AhpF, Dps). The corresponding genes are under control of the OxyR transcriptional regulator which is activated by oxidative stress. Further experiments demonstrated that osmotic stress exerted by various carbohydrates leads to an upregulation of proteins belonging to the oxyR regulon. The data suggest that the upregulated proteins enable intestinal E. coli to better cope with diet-induced osmotic stress. These examples demonstrate that gnotobiotic animal models are a valuable tool for studying diet-induced changes at the community and the

Full Text Available The importance of the gutmicrobiota to health is becoming more widely appreciated. The range of commensal microorganisms in healthy individuals and in patients with a variety of digestive diseases is under active investigation, and evidence is accumulating to suggest that both the diversity and balance of bacterial species are important for health. Disturbance of the balance of microorganisms – dysbiosis – is associated with obesity and a variety of diseases. Restoring the balance by modulating the microbiota through diet, probiotics, or drugs is now being developed as a potential treatment for digestive diseases. Rifaximin has been shown to increase levels of beneficial bacterial species without perturbing the overall composition of the microbiota in patients with a variety of digestive diseases, making it a ‘eubiotic’ rather than an antibiotic. Rifaximin has demonstrated clinical benefit in the treatment of symptomatic uncomplicated diverticular disease, where changes in the colonic microbiota contribute to the pathogenesis of this disease. Modulating the microbiota is also a promising treatment for some types of irritable bowel syndrome (IBS that have been linked to an overgrowth of coliform and Aeromonas species in the small intestine. Rifaximin has demonstrated efficacy in relieving symptoms and reducing relapses in diarrhoeal IBS in the TARGET-1, 2, and 3 trials, without reducing microbial diversity or increasing antimicrobial resistance. While many aspects of the balance of gutmicrobiota in disease are not yet fully understood, the new understanding of rifaximin as a modulator of gutmicrobiota may open up new treatment options in digestive disease.

Full Text Available The human microbiota is a hot topic at present because increasing evidences demonstrate that it should be considered an organ based on its importance to human health. Dysbiosis of the gutmicrobiota is significantly related to many human disorders. In turn, correcting such imbalances and taking advantage of gut microbes are possible methods for alleviating or even curing host diseases. A recent study published in Cell indicated that inhibition of gut microbial production of trimethylamine(TMA specifically prevents atherosclerosis in vivo. Another study found that a diet supplemented with TMA N-oxide (TMAO increased the level of atherosclerosis in mice, which suggested TMAO might be a causative factor in cardiovascular disease (CVD. However, direct inhibition of flavin-containing monooxygenase (FMO3, a hepatic enzyme that catalyzes the conversion of TMA to TMAO, results in TMA accumulation and several unpleasant side effects. The small-molecule 3, 3-dimethyl-1-butanol (DMB, identified by Wang et al., reduces TMAO through non-lethal inhibition of microbial TMA formation in mice, even when fed a western diet, including high choline. DMB is a non-toxic compound found naturally in foods such as olive oil and red wine. Therefore, the risk of CVD could be reduced by some dietary habits (such as a Mediterranean diet, which might stem from changes in gutmicrobiota. Although the impact of DMB on microbial TMA has only been observed in mouse models, it provides a guideline for the treatment of CVD in humans by regulating gut microbes. There are many similar studies that target gut microbes to treat host disorders. For example, Sarkis’ group verified that a human commensal bacterium could improve autism spectrum disorder (ASD-related gastrointestinal deficits and behavioral abnormalities in mice, which indicated that microbiome-mediated therapies might be a safe and effective treatment for ASD. In addition, fecal microbiota transplantation, which has

Gutmicrobiota is a determining factor in human physiological functions and health. It is commonly accepted that diet has a major influence on the gut microbial community, however, the effects of diet is not fully understood. The typical Mongolian diet is characterized by high and frequent consumption of fermented dairy products and red meat, and low level of carbohydrates. In this study, the gutmicrobiota profile of 26 Mongolians whom consumed wheat, rice and oat as the sole carbohydrate staple food for a week each consecutively was determined. It was observed that changes in staple carbohydrate rapidly (within a week) altered gut microbial community structure and metabolic pathway of the subjects. Wheat and oat favored bifidobacteria (Bifidobacterium catenulatum, Bifodobacteriumbifidum, Bifidobacterium adolescentis); whereas rice suppressed bifidobacteria (Bifidobacterium longum, Bifidobacterium adolescentis) and wheat suppresses Lactobaciilus, Ruminococcus and Bacteroides. The study exhibited two gut microbial clustering patterns with the preference of fucosyllactose utilization linking to fucosidase genes (glycoside hydrolase family classifications: GH95 and GH29) encoded by Bifidobacterium, and xylan and arabinoxylan utilization linking to xylanase and arabinoxylanase genes encoded by Bacteroides. There was also a correlation between Lactobacillus ruminis and sialidase, as well as Butyrivibrio crossotus and xylanase/xylosidase. Meanwhile, a strong concordance was found between the gastrointestinal bacterial microbiome and the intestinal virome. Present research will contribute to understanding the impacts of the dietary carbohydrate on human gut microbiome, which will ultimately help understand relationships between dietary factor, microbial populations, and the health of global humans. PMID:28377764

Although precise mechanisms responsible for all demonstrations of probiotic health benefits are not known, many lines of evidence suggest that probiotics function through direct or indirect impact on colonizing microbiota of the gut. Probiotics can directly influence colonizing microbes through multiple mechanisms, including the production of inhibitory compounds (bacteriocins, short chain fatty acids, and others), by producing substrates that might promote the growth of colonizing microbes (secreted exopolysaccharides, vitamins, fatty acids, sugars from undigested carbohydrates and others), and by promoting immune responses against specific microbes. Indirectly, probiotics can influence colonizing microbes by inhibiting attachment through stimulated mucin production, reinforcing gut barrier effects, and downregulation of gut inflammation, thereby promoting microbes that are associated with a healthier gut physiology. Although the value of targeted changes in populations of gut bacteria is a matter of debate, increased levels of Bifidobacterium and Lactobacillus in the gut correlate with numerous health endpoints. Microbiota changes due to probiotic intake include increased numbers of related phylotypes, decreasing pathogens and their toxins, altering bacterial community structure to enhance evenness, stabilizing bacterial communities when perturbed (eg, with antibiotics), or promoting a more rapid recovery from a perturbation. Further research will provide insight into the degree of permanence of probiotic-induced changes, although research to date suggests that continued probiotic consumption is needed for sustained impact.

The composition of the gut microbiome represents a very important environmental factor that influences the development of type 1 diabetes (T1D). We have previously shown that MyD88-deficient non-obese diabetic (MyD88-/-NOD) mice, that were protected from T1D development, had a different composition of gutmicrobiota compared to wild type NOD mice. The aim of our study was to investigate whether this protection could be transferred. We demonstrate that transfer of gutmicrobiota from diabetes-protected MyD88-deficient NOD mice, reduced insulitis and significantly delayed the onset of diabetes. Gut bacteria from MyD88-deficient mice, administered over a 3-week period, starting at 4 weeks of age, stably altered the family composition of the gut microbiome, with principally Lachnospiraceae and Clostridiaceae increased and Lactobacillaceae decreased. The transferred mice had a higher concentration of IgA and TGFβ in the lumen that was accompanied by an increase in CD8(+)CD103(+) and CD8αβ T cells in the lamina propria of the large intestine. These data indicate not only that gut bacterial composition can be altered after the neonatal/weaning period, but that the composition of the microbiome affects the mucosal immune system and can delay the development of autoimmune diabetes. This result has important implications for the development of probiotic treatment for T1D.

The human gastrointestinal tract harbors a complex and abundant microbial community reaching as high as 10(13)-10(14) microorganisms in the colon. This endogenous microbiota forms a symbiotic relationship with their eukaryotic host and this close partnership helps maintain homeostasis by performing essential and non-redundant tasks (e.g. nutrition/energy and, immune system balance, pathogen exclusion). Although this relationship is essential and beneficial to the host, various events (e.g. infection, diet, stress, inflammation) may impact microbial composition, leading to the formation of a dysbiotic microbiota, further impacting on health and disease states. For example, Crohn's disease and ulcerative colitis, collectively termed inflammatory bowel diseases (IBD), have been associated with the establishment of a dysbiotic microbiota. In addition, extra-intestinal disorders such as obesity and metabolic syndrome are also associated with the development of a dysbiotic microbiota. Consequently, there is an increasing interest in harnessing the power of the microbiome and modulating its composition as a means to alleviate intestinal pathologies/disorders and maintain health status. In this review, we will discuss the emerging relationship between the microbiota and development of colorectal cancer as well as present evidence that microbial manipulation (probiotic, prebiotic) impacts disease development.

The gutmicrobiota has been designated as an active regulator of glucose metabolism and metabolic phenotype in a number of animal and human observational studies. We evaluated the effect of removing as many bacteria as possible by antibiotics on postprandial physiology in healthy humans. Meal tests...... with measurements of postprandial glucose tolerance and postprandial release of insulin and gut hormones were performed before, immediately after and 6 weeks after a 4-day, broad-spectrum, per oral antibiotic cocktail (vancomycin 500 mg, gentamycin 40 mg and meropenem 500 mg once-daily) in a group of 12 lean...... and glucose tolerant males. Faecal samples were collected for culture-based assessment of changes in gutmicrobiota composition. Acute and dramatic reductions in the abundance of a representative set of gut bacteria was seen immediately following the antibiotic course, but no changes in postprandial glucose...

The gutmicrobiota interacts with the host via neuroimmune, neuroendocrine and neural pathways. These pathways are components of the brain-gut-microbiota axis and preclinical evidence suggests that the microbiota can recruit this bidirectional communication system to modulate brain development, func

Full Text Available The intestine and the intestinal immune system have evolved through a symbiotic homeostasis under which a highly diverse microbial flora is maintained in the gastrointestinal tract while pathogenic bacteria are recognized and eliminated. Disruption of the balance between the immune system and the gutmicrobiota results in the development of multiple pathologies in humans. Inflammatory bowel diseases have been associated with alterations in the composition of intestinal flora but whether these changes are causal or result of inflammation is still under dispute. Various chemical and genetic models of inflammatory bowel diseases have been developed and utilized to elucidate the complex relationship between intestinal epithelium, immune system and the gutmicrobiota. In this review we describe some of the most commonly used mouse models of colitis and Crohn’s disease and summarize the current knowledge of how changes in microbiota composition may affect intestinal disease pathogenesis. The pursuit of gut-microbiota interactions will no doubt continue to provide invaluable insight into the complex biology of inflammatory bowel diseases.

Metabolic disorders, including obesity, diabetes, and cardiovascular disease, are widespread in Westernized nations. Gutmicrobiota composition is a contributing factor to the susceptibility of an individual to the development of these disorders; therefore, altering a person's microbiota may ameliorate disease. One potential microbiome-altering strategy is the incorporation of modified bacteria that express therapeutic factors into the gutmicrobiota. For example, N-acylphosphatidylethanolamines (NAPEs) are precursors to the N-acylethanolamide (NAE) family of lipids, which are synthesized in the small intestine in response to feeding and reduce food intake and obesity. Here, we demonstrated that administration of engineered NAPE-expressing E. coli Nissle 1917 bacteria in drinking water for 8 weeks reduced the levels of obesity in mice fed a high-fat diet. Mice that received modified bacteria had dramatically lower food intake, adiposity, insulin resistance, and hepatosteatosis compared with mice receiving standard water or control bacteria. The protective effects conferred by NAPE-expressing bacteria persisted for at least 4 weeks after their removal from the drinking water. Moreover, administration of NAPE-expressing bacteria to TallyHo mice, a polygenic mouse model of obesity, inhibited weight gain. Our results demonstrate that incorporation of appropriately modified bacteria into the gutmicrobiota has potential as an effective strategy to inhibit the development of metabolic disorders.

To explore the relationship of gutmicrobiota with the development of type 2 diabetes (T2DM), we analyzed 121 subjects who were divided into 3 groups based on their glucose intolerance status: normal glucose tolerance (NGT; n = 44), prediabetes (Pre-DM; n = 64), or newly diagnosed T2DM (n = 13). Gutmicrobiota characterizations were determined with 16S rDNA-based high-throughput sequencing. T2DM-related dysbiosis was observed, including the separation of microbial communities and a change of alpha diversity between the different glucose intolerance statuses. To assess the correlation between metabolic parameters and microbiota diversity, clinical characteristics were also measured and a significant association between metabolic parameters (FPG, CRP) and gutmicrobiota was found. In addition, a total of 28 operational taxonomic units (OTUs) were found to be related to T2DM status by the Kruskal-Wallis H test, most of which were enriched in the T2DM group. Butyrate-producing bacteria (e.g. Akkermansia muciniphila ATCCBAA-835, and Faecalibacterium prausnitzii L2-6) had a higher abundance in the NGT group than in the pre-DM group. At genus level, the abundance of Bacteroides in the T2DM group was only half that of the NGT and Pre-DM groups. Previously reported T2DM-related markers were also compared with the data in this study, and some inconsistencies were noted. We found that Verrucomicrobiae may be a potential marker of T2DM as it had a significantly lower abundance in both the pre-DM and T2DM groups. In conclusion, this research provides further evidence of the structural modulation of gutmicrobiota in the pathogenesis of diabetes.

A healthy gutmicrobiota plays many crucial functions in the host, being involved in the correct development and functioning of the immune system, assisting in the digestion of certain foods and in the production of health-beneficial bioactive metabolites or 'pharmabiotics'. These include bioactive lipids (including SCFA and conjugated linoleic acid) antimicrobials and exopolysaccharides in addition to nutrients, including vitamins B and K. Alterations in the composition of the gutmicrobiota and reductions in microbial diversity are highlighted in many disease states, possibly rendering the host susceptible to infection and consequently negatively affecting innate immune function. Evidence is also emerging of microbially produced molecules with neuroactive functions that can have influences across the brain-gut axis. For example, γ-aminobutyric acid, serotonin, catecholamines and acetylcholine may modulate neural signalling within the enteric nervous system, when released in the intestinal lumen and consequently signal brain function and behaviour. Dietary supplementation with probiotics and prebiotics are the most widely used dietary adjuncts to modulate the gutmicrobiota. Furthermore, evidence is emerging of the interactions between administered microbes and dietary substrates, leading to the production of pharmabiotics, which may directly or indirectly positively influence human health.

The human intestinal tract is colonised by a complex community of microbes, which can have major impacts on host health. Recent research on the gutmicrobiota has largely been driven by the advent of modern sequence-based techniques, such as metagenomics. Although these are powerful and valuable tools, they have limitations. Traditional culturing and phylogeny can mitigate some of these limitations, either by expanding reference databases or by assigning functionality to specific microbial lineages. As such, culture and phylogeny will continue to have crucially important roles in human microbiota research, and will be required for the development of novel therapeutics.

Gut microbial communities often contain many Bacteroides or their close relatives, Prevotella, but not both. Prevotella strains are associated with plant-rich diets but are also linked with chronic inflammatory conditions. In 2015, papers probed the genomic diversity of Prevotella strains and interactions of Prevotella copri with its host and other bacteria.

There has been a dramatic rise in the prevalence of IgE-mediated food allergy over recent decades, particularly among infants and young children. The cause of this increase is unknown but one putative factor is a change in the composition, richness and balance of the microbiota that colonize the human gut during early infancy. The coevolution of the human gastrointestinal tract and commensal microbiota has resulted in a symbiotic relationship in which gutmicrobiota play a vital role in early life immune development and function, as well as maintenance of gut wall epithelial integrity. Since IgE mediated food allergy is associated with immune dysregulation and impaired gut epithelial integrity there is substantial interest in the potential link between gutmicrobiota and food allergy. Although the exact link between gutmicrobiota and food allergy is yet to be established in humans, recent experimental evidence suggests that specific patterns of gutmicrobiota colonization may influence the risk and manifestations of food allergy. An understanding of the relationship between gutmicrobiota and food allergy has the potential to inform both the prevention and treatment of food allergy. In this paper we review the theory and evidence linking gutmicrobiota and IgE-mediated food allergy in early life. We then consider the implications and challenges for future research, including the techniques of measuring and analyzing gutmicrobiota, and the types of studies required to advance knowledge in the field.

Full Text Available There has been a dramatic rise in the prevalence of IgE-mediated food allergy over recent decades, particularly among infants and young children. The cause of this increase is unknown but one putative factor is a change in the composition, richness and balance of the microbiota that colonize the human gut during early infancy. The coevolution of the human gastrointestinal tract and commensal microbiota has resulted in a symbiotic relationship in which gutmicrobiota play a vital role in early life immune development and function, as well as maintenance of gut wall epithelial integrity. Since IgE mediated food allergy is associated with immune dysregulation and impaired gut epithelial integrity there is substantial interest in the potential link between gutmicrobiota and food allergy. Although the exact link between gutmicrobiota and food allergy is yet to be established in humans, recent experimental evidence suggests that specific patterns of gutmicrobiota colonization may influence the risk and manifestations of food allergy. An understanding of the relationship between gutmicrobiota and food allergy has the potential to inform both the prevention and treatment of food allergy. In this paper we review the theory and evidence linking gutmicrobiota and IgE-mediated food allergy in early life. We then consider the implications and challenges for future research, including the techniques of measuring and analyzing gutmicrobiota, and the types of studies required to advance knowledge in the field.

The prevalence of obesity is rapidly becoming endemic in industrialized countries and continues to increase in developing countries worldwide. Obesity predisposes people to an increased risk of developing metabolic syndrome. Recent studies have described an association between obesity and certain gutmicrobiota, suggesting that gutmicrobiota might play a critical role in the development of obesity. Although probiotics have many beneficial health effects in humans and animals, attention has only recently been drawn to manipulating the gutmicrobiota, such as lactic acid bacteria (LAB), to influence the development of obesity. In this review, we first describe the causes of obesity, including the genetic and environmental factors. We then describe the relationship between the gutmicrobiota and obesity, and the mechanisms by which the gutmicrobiota influence energy metabolism and inflammation in obesity. Lastly, we focus on the potential role of LAB in mediating the effects of the gutmicrobiota in the development of obesity.

Full Text Available Early colonization of the infant gastrointestinal tract is crucial for the overall health of the infant, and establishment and maintenance of non-pathogenic intestinal microbiota may reduce several neonatal inflammatory conditions. Much effort has therefore been devoted to manipulation of the composition of the microbiota through 1 the role of early infant nutrition, particularly breast milk, and supplementation of infant formula with prebiotics that positively influence the enteric microbiota by selectively promoting growth of beneficial bacteria and 2 oral administration of probiotic bacteria which when administered in adequate amounts confer a health benefit on the host. While the complex microbiota of the adult is difficult to change in the long-term, there is greater impact of the diet on infant microbiota as this is not as stable as in adults. Decreasing excessive use of antibiotics and increasing the use of pre- and probiotics have shown to be beneficial in the prevention of several important infant diseases such as necrotizing enterocolitis and atopic eczema as well as improvement of short and long-term health. This review addresses how the composition of the gutmicrobiota becomes established in early life, its relevance to infant health, and dietary means by which it can be manipulated.

The intestinal microbiota is a large and diverse microbial community that inhabits the intestine, containing about 100 trillion bacteria of 500-1000 distinct species that, collectively, provide benefits to the host. The human gutmicrobiota composition is determined by a myriad of factors, among them genetic and environmental, including diet and medication. The microbiota contributes to nutrient absorption and maturation of the immune system. As reciprocity, the host immune system plays a central role in shaping the composition and localization of the intestinal microbiota. Secretory immunoglobulins A (sIgAs), component of the adaptive immune system, are important player in the protection of epithelium, and are known to have an important impact on the regulation of microbiota composition. A recent study published in Immunity by Fransen and colleagues aimed to mechanistically decipher the interrelationship between sIgA and microbiota diversity/composition. This commentary will discuss these important new findings, as well as how future therapies can ultimately benefit from such discovery.

Full Text Available The intimate interplay between immune system, metabolism and gutmicrobiota plays an important role in controlling metabolic homeostasis and possible obesity development. Obesity involves impairment of immune response affecting both innate and adaptive immunity. The main factors involved in the relationship of obesity with inflammation have not been completely elucidated. On the other hand, gutmicrobiota, via innate immune receptors, has emerged as one of the key factors regulating events triggering acute inflammation associated with obesity and metabolic syndrome. Inflammatory disorders lead to several signalling transduction pathways activation, inflammatory cytokine, chemokine production and cell migration, which in turn cause metabolic dysfunction. Inflamed adipose tissue, with increased macrophages infiltration, is associated with impaired preadipocyte development and differentiation to mature adipose cells, leading to ectopic lipid accumulation and insulin resistance. This review focuses on the relationship between obesity and inflammation, which is essential to understand the pathological mechanisms governing metabolic syndrome.

Birds represent a diverse and evolutionarily successful lineage, occupying a wide range of niches throughout the world. Like all vertebrates, avians harbor diverse communities of microorganisms within their guts, which collectively fulfill crucial roles in providing the host with nutrition and protection from pathogens. Across the field of avian microbiology knowledge is extremely uneven, with several species accounting for an overwhelming majority of all microbiological investigations. These include agriculturally important birds, such as chickens and turkeys, as well as birds of evolutionary or conservation interest. In our previous study we attempted the first meta-analysis of the avian gutmicrobiota, using 16S rRNA gene sequences obtained from a range of publicly available data sets. We have now extended our analysis to explore the microbiology of several key species in detail, to consider the avian microbiota within the context of what is known about other vertebrates, and to identify key areas of interest in avian microbiology for future study.

Human beings harbor gut microbial communities that are essential to preserve human health. Molded by the human genome, the gutmicrobiota (GM) is an adaptive component of the human superorganisms that allows host adaptation at different timescales, optimizing host physiology from daily life to lifespan scales and human evolutionary history. The GM continuously changes from birth up to the most extreme limits of human life, reconfiguring its metagenomic layout in response to daily variations in diet or specific host physiological and immunological needs at different ages. On the other hand, the microbiota plasticity was strategic to face changes in lifestyle and dietary habits along the course of the recent evolutionary history, that has driven the passage from Paleolithic hunter-gathering societies to Neolithic agricultural farmers to modern Westernized societies. PMID:25408692

Human beings harbor gut microbial communities that are essential to preserve human health. Molded by the human genome, the gutmicrobiota (GM) is an adaptive component of the human superorganisms that allows host adaptation at different timescales, optimizing host physiology from daily life to lifespan scales and human evolutionary history. The GM continuously changes from birth up to the most extreme limits of human life, reconfiguring its metagenomic layout in response to daily variations in diet or specific host physiological and immunological needs at different ages. On the other hand, the microbiota plasticity was strategic to face changes in lifestyle and dietary habits along the course of the recent evolutionary history, that has driven the passage from Paleolithic hunter-gathering societies to Neolithic agricultural farmers to modern Westernized societies.

Emerging evidence has suggested a potential impact of gutmicrobiota on the pathophysiology of heart failure (HF). However, it is still unknown whether HF is associated with dysbiosis in gutmicrobiota. We investigated the composition of gutmicrobiota in patients with HF to elucidate whether gut microbial dysbiosis is associated with HF. We performed 16S ribosomal RNA gene sequencing of fecal samples obtained from 12 HF patients and 12 age-matched healthy control (HC) subjects, and analyzed the differences in gutmicrobiota. We further compared the composition of gutmicrobiota of 12 HF patients younger than 60 years of age with that of 10 HF patients 60 years of age or older. The composition of gut microbial communities of HF patients was distinct from that of HC subjects in both unweighted and weighted UniFrac analyses. Eubacterium rectale and Dorea longicatena were less abundant in the gutmicrobiota of HF patients than in that of HC subjects. Compared to younger HF patients, older HF patients had diminished proportions of Bacteroidetes and larger quantities of Proteobacteria. The genus Faecalibacterium was depleted, while Lactobacillus was enriched in the gutmicrobiota of older HF patients. These results suggest that patients with HF harbor significantly altered gutmicrobiota, which varies further according to age. New concept of heart-gut axis has a great potential for breakthroughs in the development of novel diagnostic and therapeutic approach for HF.

Increasing evidence suggests that gutmicrobiota is an environmental factor that plays a crucial role in obesity. However, the aetiology of obesity is rather complex and depends on different factors. Furthermore, there is a lack of consensus about the exact role that this microbial community plays i

The rapid rise in childhood allergies (atopy) in Westernized nations has implicated associated environmental exposures and lifestyles as primary drivers of disease development. Culture-based microbiological studies indicate that atopy has demonstrable ties to altered gut microbial colonization in very early life. Infants who exhibit more severe multisensitization to food- or aero-allergens have a significantly higher risk of subsequently developing asthma in childhood. Hence an emerging hypothesis posits that environment- or lifestyle-driven aberrancies in the early-life gut microbiome composition and by extension, microbial function, represent a key mediator of childhood allergic asthma. Animal studies support this hypothesis. Environmental microbial exposures epidemiologically associated with allergy protection in humans confer protection against airway allergy in mice. In addition, gut microbiome-derived short-chain fatty acids produced from a high-fiber diet have been shown to protect against allergy via modulation of both local and remote mucosal immunity as well as hematopoietic antigen-presenting cell populations. Here we review key data supporting the concept of a gut-airway axis and its critical role in childhood atopy.

The prevalence of obesity has increased epidemically during the past four decades and worldwide more than half a billion adults are now obese. Obesity increases the risk of type 2 diabetes, cardiovascular diseases and cancer, which are among the leading causes of death worldwide. Thus, effective ...... for prevention. The main purpose of this PhD was to explore the effect of dietary modulation of the gutmicrobiota on disease markers in obese individuals....

Full Text Available Some evidence suggests that bone health can be regulated by gutmicrobiota. To better understand this, we performed 16S ribosomal RNA sequencing to analyze the intestinal microbial diversity in primary osteoporosis (OP patients, osteopenia (ON patients and normal controls (NC. We observed an inverse correlation between the number of bacterial taxa and the value of bone mineral density. The diversity estimators in the OP and ON groups were increased compared with those in the NC group. Beta diversity analyses based on hierarchical clustering and principal coordinate analysis (PCoA could discriminate the NC samples from OP and ON samples. Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria constituted the four dominant phyla in all samples. Proportion of Firmicutes was significantly higher and Bacteroidetes was significantly lower in OP samples than that in NC samples (p gut microbiota may be a critical factor in osteoporosis development, which can further help us search for novel biomarkers of gutmicrobiota in OP and understand the interaction between gutmicrobiota and bone health.

The gastrointestinal (GI) tract is teeming with an extremely abundant and diverse microbial community. The members of this community have coevolved along with their hosts over millennia. Until recently, the gut ecosystem was viewed as black box with little knowledge of who or what was there or their specific functions. Over the past decade, however, this ecosystem has become one of fastest growing research areas of focus in microbial ecology and human and animal physiology. This increased interest is largely in response to studies tying microbes in the gut to important diseases afflicting modern society, including obesity, allergies, inflammatory bowel diseases, and diabetes. Although the importance of a resident community of microorganisms in health was first hypothesized by Pasteur over a century ago (Sears, 2005), the multiplicity of physiological changes induced by commensal bacteria has only recently been recognized (Hooper et al., 2001). The term 'ecological development' was recently coined to support the idea that development of the GI tract is a product of the genetics of the host and the host's interactions with resident microbes (Hooper, 2004). The search for new therapeutic targets and disease biomarkers has escalated the need to understand the identities and functions of the microorganisms inhabiting the gut. Recent studies have revealed new insights into the membership of the gut microbial community, interactions within that community, as well as mechanisms of interaction with the host. This chapter focuses on the microbial ecology of the gut, with an emphasis on information gleaned from recent molecular studies.

Conventional studies reveal a contributory role of gutmicrobiota in the process of diabetes mellitus (DM) and end-stage renal disease (ESRD). However, the mechanism through which gutmicrobiota influence diabetic kidney disease (DKD) is ignored. In the present article, we reviewed the changes in gutmicrobiota of patients with DM, DKD as well as ESRD, and how this may contribute to the progression of DKD. Although further studies are needed to either selectively change the composition of the...

Gutmicrobiota has been recently established to have a contributory role in the development of cardiometabolic disorders, such as atherosclerosis, obesity, and type 2 diabetes. Growing interest has focused on the modulation of gutmicrobiota as a therapeutic strategy in cardiovascular diseases and metabolic disorders. In this paper, we have reviewed the impact of gutmicrobiota on metabolic disorders and cardiovascular disease risk, focusing on the newest findings in this field.

Numerous studies of rodents suggest that the gutmicrobiota populations are sensitive to genetic and environmental influences, and can produce or influence afferent signals that directly or indirectly impinge on energy homeostatic systems affecting both energy balance (weight gain or loss) and energy stores. Fecal transplants from obese and lean human, and from mouse donors to gnotobiotic mice, result in adoption of the donor somatotype by the formerly germ-free rodents. Thus, the microbiota is certainly implicated in the development of obesity, adiposity-related comorbidities, and the response to interventions designed to achieve sustained weight reduction in mice. More studies are needed to determine whether the microbiota plays a similarly potent role in human body-weight regulation and obesity.

Over the last 10-15 years, our understanding of the composition and functions of the human gutmicrobiota has increased exponentially. To a large extent, this has been due to new 'omic' technologies that have facilitated large-scale analysis of the genetic and metabolic profile of this microbial community, revealing it to be comparable in influence to a new organ in the body and offering the possibility of a new route for therapeutic intervention. Moreover, it might be more accurate to think of it like an immune system: a collection of cells that work in unison with the host and that can promote health but sometimes initiate disease. This review gives an update on the current knowledge in the area of gut disorders, in particular metabolic syndrome and obesity-related disease, liver disease, IBD and colorectal cancer. The potential of manipulating the gutmicrobiota in these disorders is assessed, with an examination of the latest and most relevant evidence relating to antibiotics, probiotics, prebiotics, polyphenols and faecal microbiota transplantation.

Full Text Available Dietary polyphenols present in a broad range of plant foods have been related to beneficial health effects. This review aims to update the current information about the modulation of the gutmicrobiota by dietary phenolic compounds, from a perspective based on the experimental approaches used. After referring to general aspects of gutmicrobiota and dietary polyphenols, studies related to this topic are presented according to their experimental design: batch culture fermentations, gastrointestinal simulators, animal model studies, and human intervention studies. In general, studies evidence that dietary polyphenols may contribute to the maintenance of intestinal health by preserving the gut microbial balance through the stimulation of the growth of beneficial bacteria (i.e., lactobacilli and bifidobacteria and the inhibition of pathogenic bacteria, exerting prebiotic-like effects. Combination of in vitro and in vivo models could help to understand the underlying mechanisms in the polyphenols-microbiota-host triangle and elucidate the implications of polyphenols on human health. From a technological point of view, supplementation with rich-polyphenolic stuffs (phenolic extracts, phenolic-enriched fractions, etc. could be an effective option to improve health benefits of functional foods such as the case of dairy fermented foods.

Human adolescence is arguably one of the most challenging periods of development. The young adult is exposed to a variety of stressors and environmental stimuli on a backdrop of significant physiological change and development, which is especially apparent in the brain. It is therefore unsurprising that many psychiatric disorders are first observable during this time. The human intestine is inhabited by trillions of microorganisms, and evidence from both preclinical and clinical research focusing on the established microbiota-gut-brain axis suggests that the etiology and pathophysiology of psychiatric disorders may be influenced by intestinal dysbiosis. Provocatively, many if not all of the challenges faced by the developing teen have a documented impact on these intestinal commensal microbiota. In this review, we briefly summarize what is known about the developing adolescent brain and intestinal microbiota, discuss recent research investigating the microbiota-gut-brain axis during puberty, and propose that pre- and probiotics may prove useful in both the prevention and treatment of psychiatric disorders specifically benefitting the young adult.

The microbiome, of which the bacterial component alone (microbiota), is estimated to include 10 times more cells than human cells of the body, blooms immediately after birth and evolves in composition and complexity throughout childhood. The gut microbiome has a profound impact on gastrointestinal tract development, maintenance of mucosal surface integrity, and contributes to the nutritional status of the host and thus plays a pivotal role in health and disease. New technologies have enabled the detailed characterization of normal microbial symbionts and dysbiosis-disease associations. This review summarizes the stepwise establishment of the intestinal microbiota, influential environmental factors, and how this may be perturbed in preterm very-low-birth-weight infants. The contribution of the microbiota to provision of energy and nutrients for intestinal development and the nutritional status of the host are reviewed. In addition, the crucial role of the gutmicrobiota in maintaining mucosal integrity is explored along with how its breakdown can lead to sepsis, necrotizing enterocolitis, and systemic inflammatory response syndrome. Finally, the role of enteral feeding type (human milk, formula, and nutrient fortification) in mediating these processes is discussed, and guidance is provided for nutritional strategies to promote health in these fragile infants.

Transferring gutmicrobiota from one individual to another may enable researchers to "humanize" the gut of animal models and transfer phenotypes between species. To date, most studies of gutmicrobiota transfer are performed in germ-free mice. In the studies presented, it was tested whether an antibiotic treatment approach could be used instead. C57BL/6 mice were treated with ampicillin prior to inoculation at weaning or eight weeks of age with gutmicrobiota from lean or obese donors. The gutmicrobiota and clinical parameters of the recipients was characterized one and six weeks after inoculation. The results demonstrate, that the donor gutmicrobiota was introduced, established, and changed the gutmicrobiota of the recipients. Six weeks after inoculation, the differences persisted, however alteration of the gutmicrobiota occurred with time within the groups. The clinical parameters of the donor phenotype were partly transmissible from obese to lean mice, in particularly β cell hyperactivity in the obese recipients. Thus, a successful inoculation of gutmicrobiota was not age dependent in order for the microbes to colonize, and transferring different microbial compositions to conventional antibiotic-treated mice was possible at least for a time period during which the microbiota may permanently modulate important host functions.

Full Text Available The growing demand for wood has resulted in large volumes of wood wastes that are daily released to the soil from the activities of sawmills in South-Western Nigeria. In an attempt to setup a bioremediation model for sawdust, this study therefore aimed at evaluating microbial diversity, and the level of digestive enzymes in the gut of earthworms (Eudrilus eugeniae, Libyodrilus violaceous and Hyperiodrilus africanus of sawmill origin. Four major sawmills located in Abeokuta (7o9’12” N - 3o19’35” E, namely Lafenwa, Sapon, Isale-Ake and Kotopo sawmills were used for this study. The arboretum of the Federal University of Agriculture, Abeokuta was used as control. Gut microbial analysis was carried out using the pour-plate method while digestive enzyme activities in the earthwormguts were done by the spectrophotometric method. Higher microbial counts (28.5±0.1x10³-97.0±0.1x10³cfu for bacteria and 7.0±0.1x10³-96.0±0.1x10³cfu for fungi and microbial diversity were recorded in the gut of earthworms of the sawmill locations than those of the control site (17.5±0.1x10³cfu for bacteria and 4.5±0.1x10³cfu for fungi. Streptococcus mutans and Proteus spp.were common in the gut of E. eugeniae, and L. violaceous from the study sawmills, while Streptococcus mutans were also identified in H. africanus, but absent in the gut of E. eugeniae from the control site. Cellulase (48.67±0.02mg/g and lipase (1.81±0.01mg/g activities were significantly higher (p<0.05 in the gut of earthworms from the control site than those of the study sawmills. Furthermore, amylase (α and β activity was highest in the gut of earthworms from the sawmills. Variations observed in the gut microbial and digestive enzyme activities of earthworms from the study sawmills as compared to the control site suggests that earthworms, especially E. eugeniae, could be a better organism for use as bioremediator of wood wastes. Rev. Biol. Trop. 62 (3: 1241-1249. Epub 2014 September

Full Text Available Obesity is the main condition that is correlated with the appearance of insulin resistance, which is the major link among its comorbidities, such as type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular and neurodegenerative diseases, and several types of cancer. Obesity affects a large number of individuals worldwide; it degrades human health and quality of life. Here, we review the role of the gutmicrobiota in the pathophysiology of obesity and type 2 diabetes, which is promoted by a bacterial diversity shift mediated by overnutrition. Whole bacteria, their products, and metabolites undergo increased translocation through the gut epithelium to the circulation due to degraded tight junctions and the consequent increase in intestinal permeability that culminates in inflammation and insulin resistance. Several strategies focusing on modulation of the gutmicrobiota (antibiotics, probiotics, and prebiotics are being experimentally employed in metabolic derangement in order to reduce intestinal permeability, increase the production of short chain fatty acids and anorectic gut hormones, and promote insulin sensitivity to counteract the inflammatory status and insulin resistance found in obese individuals.

In the last decade the impressive expansion of our knowledge of the vast microbial community that resides in the human intestine, the gutmicrobiota, has provided support to the concept that a disturbed intestinal ecology might promote development and maintenance of symptoms in irritable bowel syndrome (IBS). As a correlate, manipulation of gutmicrobiota represents a new strategy for the treatment of this multifactorial disease. A number of attempts have been made to modulate the gut bacterial composition, following the idea that expansion of bacterial species considered as beneficial (Lactobacilli and Bifidobacteria) associated with the reduction of those considered harmful (Clostridium, Escherichia coli, Salmonella, Shigella and Pseudomonas) should attenuate IBS symptoms. In this conceptual framework, probiotics appear an attractive option in terms of both efficacy and safety, while prebiotics, synbiotics and antibiotics still need confirmation. Fecal transplant is an old treatment translated from the cure of intestinal infective pathologies that has recently gained a new life as therapeutic option for those patients with a disturbed gut ecosystem, but data on IBS are scanty and randomized, placebo-controlled studies are required.

Full Text Available In recent years, the increase in human microbiome research brought about by the rapidly evolving “omic” technologies has established that the balance among the microbial groups present in the human gut, and their multipronged interactions with the host, are crucial for health. On the other hand, epidemiological and experimental support has also grown for the ‘early programming hypothesis’, according to which factors that act in utero and early in life program the risks for adverse health outcomes later on. The microbiota of the gut develops during infancy, in close interaction with immune development, and with extensive variability across individuals. It follows that the specific process of gut colonization and the microbe-host interactions established in an individual during this period have the potential to represent main determinants of life-long propensity to immune disease. Although much remains to be learnt on the progression of events by which the gutmicrobiota becomes established and initiates its intimate relationships with the host, and on the long-term repercussions of this process, recent works have advanced significatively in this direction.

In the last decade the impressive expansion of our knowledge of the vast microbial community that resides in the human intestine, the gutmicrobiota, has provided support to the concept that a disturbed intestinal ecology might promote development and maintenance of symptoms in irritable bowel syndrome (IBS). As a correlate, manipulation of gutmicrobiota represents a new strategy for the treatment of this multifactorial disease. A number of attempts have been made to modulate the gut bacterial composition, following the idea that expansion of bacterial species considered as beneficial (Lactobacilli and Bifidobacteria) associated with the reduction of those considered harmful (Clostridium, Escherichia coli, Salmonella, Shigella and Pseudomonas) should attenuate IBS symptoms. In this conceptual framework, probiotics appear an attractive option in terms of both efficacy and safety, while prebiotics, synbiotics and antibiotics still need confirmation. Fecal transplant is an old treatment translated from the cure of intestinal infective pathologies that has recently gained a new life as therapeutic option for those patients with a disturbed gut ecosystem, but data on IBS are scanty and randomized, placebo-controlled studies are required. PMID:26900286

As being a necessary amino acid, taurine plays an important role in the regulation of neuroendocrine functions and nutrition. In this study, effects of taurine on mice gut microbes and metabolism were investigated. BALB/C mice were randomly divided into three experimental groups: The first group was administered saline (CK), the second was administered 165 mg/kg natural taurine (NE) and the third one administered 165 mg/kg synthetic taurine (CS). Gutmicrobiota composition in mice feces was analyzed by metagenomics technology, and the content of short-chain fatty acids (SCFA) in mice feces was detected by gas chromatography (GC), while the concentrations of lipopolysaccharide (LPS) and superoxide dismutase (SOD) were detected by a LPS ELISA kit and a SOD assay kit, respectively. The results showed that the effect of taurine on gutmicrobiota could reduce the abundance of Proteobacteria, especially Helicobacter. Moreover, we found that the SCFA content was increased in feces of the NE group while LPS content was decreased in serum of the NE group; the SOD activity in serum and livers of the NE and CS groups were not changed significantly compare to that of the CK group. In conclusion, taurine could regulate the gut micro-ecology, which might be of benefit to health by inhibiting the growth of harmful bacteria, accelerating the production of SCFA and reducing LPS concentration.

The gut epithelium is a barrier between the 'outside' and 'inside' world. The major function of the epithelium is to absorb nutrients, ions and water, yet it must balance these functions with that of protecting the 'inside' world from potentially harmful toxins, irritants, bacteria and other pathogens that also exist in the gut lumen. The health of an individual depends upon the efficient digestion and absorption of all required nutrients from the diet. This requires sensing of meal components by gut enteroendocrine cells, activation of neural and humoral pathways to regulate gastrointestinal motor, secretory and absorptive functions, and also to regulate food intake and plasma levels of glucose. In this way, there is a balance between the delivery of food and the digestive and absorptive capacity of the intestine. Maintenance of the mucosal barrier likewise requires sensory detection of pathogens, toxins and irritants; breakdown of the epithelial barrier is associated with gut inflammation and may ultimately lead to inflammatory bowel disease. However, disruption of the barrier alone is not sufficient to cause frank inflammatory bowel disease. Several recent studies have provided compelling new evidence to suggest that changes in epithelial barrier function and inflammation are associated with and may even lead to altered regulation of body weight and glucose homeostasis. This article provides a brief review of some recent evidence to support the hypothesis that changes in the gutmicrobiota and alteration of gut epithelial function will perturb the homeostatic humoral and neural pathways controlling food intake and body weight.

of allergies. Methods: We investigated whether presence of older siblings, furred pets and early life infections affected gut microbial communities at 9 and 18 months of age and whether these differences were associated with the cumulative prevalence of atopic symptoms of eczema and asthmatic bronchitis...... and the cumulative prevalence of diagnosed asthmatic bronchitis and self-reported eczema at three years of age. Results: The number of older siblings correlated positively with bacterial diversity (p = 0.030), diversity of the phyla Firmicutes (p = 0.014) and Bacteroidetes (p = 0.004) and bacterial richness (p = 0....... Gutmicrobiota characteristics were not significantly associated with cumulative occurrence of eczema and asthmatic bronchitis during the first three years of life. Conclusions: Presence of older siblings is associated with increased gut microbial diversity and richness during early childhood, which...

The prevalence of obesity has increased epidemically during the past four decades and worldwide more than half a billion adults are now obese. Obesity increases the risk of type 2 diabetes, cardiovascular diseases and cancer, which are among the leading causes of death worldwide. Thus, effective...... strategies to reduce obesity-related morbidity and mortality are essential. It has been hypothesized that the microbes in the human gut are involved in the development of obesity-related diseases and that intake of nutrients affecting the gut microbial community in specific ways, can be a new strategy...... for prevention. The main purpose of this PhD was to explore the effect of dietary modulation of the gutmicrobiota on disease markers in obese individuals....

Full Text Available BACKGROUND: Interactions between the diet and intestinal microbiota play a role in health and disease, including obesity and related metabolic complications. There is great interest to use dietary means to manipulate the microbiota to promote health. Currently, the impact of dietary change on the microbiota and the host metabolism is poorly predictable and highly individual. We propose that the responsiveness of the gutmicrobiota may depend on its composition, and associate with metabolic changes in the host. METHODOLOGY: Our study involved three independent cohorts of obese adults (n = 78 from Belgium, Finland, and Britain, participating in different dietary interventions aiming to improve metabolic health. We used a phylogenetic microarray for comprehensive fecal microbiota analysis at baseline and after the intervention. Blood cholesterol, insulin and inflammation markers were analyzed as indicators of host response. The data were divided into four training set - test set pairs; each intervention acted both as a part of a training set and as an independent test set. We used linear models to predict the responsiveness of the microbiota and the host, and logistic regression to predict responder vs. non-responder status, or increase vs. decrease of the health parameters. PRINCIPAL FINDINGS: Our models, based on the abundance of several, mainly Firmicute species at baseline, predicted the responsiveness of the microbiota (AUC = 0.77-1; predicted vs. observed correlation = 0.67-0.88. Many of the predictive taxa showed a non-linear relationship with the responsiveness. The microbiota response associated with the change in serum cholesterol levels with an AUC of 0.96, highlighting the involvement of the intestinal microbiota in metabolic health. CONCLUSION: This proof-of-principle study introduces the first potential microbial biomarkers for dietary responsiveness in obese individuals with impaired metabolic health, and reveals the

Background Interactions between the diet and intestinal microbiota play a role in health and disease, including obesity and related metabolic complications. There is great interest to use dietary means to manipulate the microbiota to promote health. Currently, the impact of dietary change on the microbiota and the host metabolism is poorly predictable and highly individual. We propose that the responsiveness of the gutmicrobiota may depend on its composition, and associate with metabolic changes in the host. Methodology Our study involved three independent cohorts of obese adults (n = 78) from Belgium, Finland, and Britain, participating in different dietary interventions aiming to improve metabolic health. We used a phylogenetic microarray for comprehensive fecal microbiota analysis at baseline and after the intervention. Blood cholesterol, insulin and inflammation markers were analyzed as indicators of host response. The data were divided into four training set – test set pairs; each intervention acted both as a part of a training set and as an independent test set. We used linear models to predict the responsiveness of the microbiota and the host, and logistic regression to predict responder vs. non-responder status, or increase vs. decrease of the health parameters. Principal Findings Our models, based on the abundance of several, mainly Firmicute species at baseline, predicted the responsiveness of the microbiota (AUC = 0.77–1; predicted vs. observed correlation = 0.67–0.88). Many of the predictive taxa showed a non-linear relationship with the responsiveness. The microbiota response associated with the change in serum cholesterol levels with an AUC of 0.96, highlighting the involvement of the intestinal microbiota in metabolic health. Conclusion This proof-of-principle study introduces the first potential microbial biomarkers for dietary responsiveness in obese individuals with impaired metabolic health, and reveals the potential of

Termites are well recognized for their thriving on recalcitrant lignocellulosic diets through nutritional symbioses with gut-dwelling microbiota; however, the effects of diet changes on termite gutmicrobiota are poorly understood, especially for the lower termites. In this study, we employed high-throughput 454 pyrosequencing of 16S V1-V3 amplicons to compare gutmicrobiotas of Tsaitermes ampliceps fed with lignin-rich and lignin-poor cellulose diets after a 2-week-feeding period. As a result, the majority of bacterial taxa were shared across the treatments with different diets, but their relative abundances were modified. In particular, the relative abundance was reduced for Spirochaetes and it was increased for Proteobacteria and Bacteroides by feeding the lignin-poor diet. The evenness of gutmicrobiota exhibited a significant difference in response to the diet type (filter paper diets microbiota and suggest that the dietary lignocellulose composition could cause shifting rapidly in the termite gutmicrobiota.

Full Text Available From birth onwards, the human gutmicrobiota rapidly increases in diversity and reaches an adult-like stage at three years of age. After this age, the composition may fluctuate in response to external factors such as antibiotics. Previous studies have shown that resilience is not complete months after cessation of the antibiotic intake. However, little is known about the short-term effects of antibiotic intake on the gut microbial community. Here we examined the load and composition of the fecal microbiota immediately after treatment in 21 patients, who received broad-spectrum antibiotics such as fluoroquinolones and β-lactams. A fecal sample was collected from all participants before treatment and one week after for microbial load and community composition analyses by quantitative PCR and pyrosequencing of the 16S rRNA gene, respectively. Fluoroquinolones and β-lactams significantly decreased microbial diversity by 25% and reduced the core phylogenetic microbiota from 29 to 12 taxa. However, at the phylum level, these antibiotics increased the Bacteroidetes/Firmicutes ratio (p = 0.0007, FDR = 0.002. At the species level, our findings unexpectedly revealed that both antibiotic types increased the proportion of several unknown taxa belonging to the Bacteroides genus, a Gram-negative group of bacteria (p = 0.0003, FDR<0.016. Furthermore, the average microbial load was affected by the treatment. Indeed, the β-lactams increased it significantly by two-fold (p = 0.04. The maintenance of or possible increase detected in microbial load and the selection of Gram-negative over Gram-positive bacteria breaks the idea generally held about the effect of broad-spectrum antibiotics on gutmicrobiota.

Clostridium difficile infection is one of the most common health care-associated infections, and up to 40% of patients suffer from recurrence of disease following standard antibiotic therapy. Recently, fecal microbiota transplantation (FMT) has been successfully used to treat recurrent C. difficile infection. It is hypothesized that FMT aids in recovery of a microbiota capable of colonization resistance to C. difficile. However, it is not fully understood how this occurs. Here we investigated changes in the fecal microbiota structure following FMT in patients with recurrent C. difficile infection, and imputed a hypothetical functional profile based on the 16S rRNA profile using a predictive metagenomic tool. Increased relative abundance of Bacteroidetes and decreased abundance of Proteobacteria were observed following FMT. The fecal microbiota of recipients following transplantation was more diverse and more similar to the donor profile than the microbiota prior to transplantation. Additionally, we observed differences in the imputed metagenomic profile. In particular, amino acid transport systems were overrepresented in samples collected prior to transplantation. These results suggest that functional changes accompany microbial structural changes following this therapy. Further identification of the specific community members and functions that promote colonization resistance may aid in the development of improved treatment methods for C. difficile infection. Within the last decade, Clostridium difficile infection has surpassed other bacterial infections to become the leading cause of nosocomial infections. Antibiotic use, which disrupts the gutmicrobiota and its capability in providing colonization resistance against C. difficile, is a known risk factor in C. difficile infection. In particular, recurrent C. difficile remains difficult to treat with standard antibiotic therapy. Fecal microbiota transplantation (FMT) has provided a successful treatment method for

Consistent with an important role for adaptive immunity in modulating interactions between intestinal bacteria and host, dramatic alteration in the composition of gut microbes during chronic HIV infection was recently reported by ourselves and independently by four other research groups. Here we evaluate our results in the context of these other studies and delve into the effects of antiretroviral therapy (ART). Although gutmicrobiota of HIV-positive individuals on ART usually does not resemble that of HIV-negative individuals, the degree to which ART restores health-associated prevalence varies across bacterial taxa. Finally, we discuss potential drivers and health consequences of gutmicrobiota alterations. We propose that understanding the mechanism of HIV-associated gutmicrobiota changes will elucidate the role of adaptive immunity in shaping gutmicrobiota composition, and lay the foundation for therapeutics targeting the microbiota to attenuate HIV disease progression and reduce the risk of gut-linked disease in people with HIV.

an antibiotic treatment approach could be used instead. C57BL/6 mice were treated with ampicillin prior to inoculation at weaning or eight weeks of age with gutmicrobiota from lean or obese donors. The gutmicrobiota and clinical parameters of the recipients was characterized one and six weeks after...... of the donor phenotype were partly transmissible from obese to lean mice, in particularly beta cell hyperactivity in the obese recipients. Thus, a successful inoculation of gutmicrobiota was not age dependent in order for the microbes to colonize, and transferring different microbial compositions......Transferring gutmicrobiota from one individual to another may enable researchers to "humanize'' the gut of animal models and transfer phenotypes between species. To date, most studies of gutmicrobiota transfer are performed in germ-free mice. In the studies presented, it was tested whether...

The interplay between the immune response and the gutmicrobiota is complex. Although it is well-established that the gutmicrobiota is essential for the proper development of the immune system, recent evidence indicates that the cells of the immune system also influence the composition of the gutmicrobiota. This interaction can have important consequences for the development of inflammatory diseases, including autoimmune diseases and allergy, and the specific mechanisms by which the gut commensals drive the development of different types of immune responses are beginning to be understood. Furthermore, sex hormones are now thought to play a novel role in this complex relationship, and collaborate with both the gutmicrobiota and immune system to influence the development of autoimmune disease. In this review, we will focus on recent studies that have transformed our understanding of the importance of the gutmicrobiota in inflammatory responses.

The gut nourishes rich bacterial communities that affect profoundly the functions of the immune system. The relationship between gutmicrobiota and the immune system is one of reciprocity. The microbiota contributes to nutrient processing and the development, maturation, and function of the immune system. Conversely, the immune system, particularly the adaptive immune system, plays a key role in shaping the repertoire of gutmicrobiota. The fitness of host immune system is reflected in the gutmicrobiota, and deficiencies in either innate or adaptive immunity impact on diversity and structures of bacterial communities in the gut. Here, we discuss the mechanisms that underlie this reciprocity and emphasize how the adaptive immune system via immunoglobulins (i.e. IgA) contributes to diversification and balance of gutmicrobiota required for immune homeostasis.

The gut microbiome is a complex and metabolically active community that directly influences host phenotypes. In this study, we profile gutmicrobiota using 16S rRNA gene sequencing in 531 well-phenotyped Finnish men from the Metabolic Syndrome In Men (METSIM) study. We investigate gutmicrobiota relationships with a variety of factors that have an impact on the development of metabolic and cardiovascular traits. We identify novel associations between gutmicrobiota and fasting serum levels of a number of metabolites, including fatty acids, amino acids, lipids, and glucose. In particular, we detect associations with fasting plasma trimethylamine N-oxide (TMAO) levels, a gutmicrobiota-dependent metabolite associated with coronary artery disease and stroke. We further investigate the gutmicrobiota composition and microbiota-metabolite relationships in subjects with different body mass index and individuals with normal or altered oral glucose tolerance. Finally, we perform microbiota co-occurrence network analysis, which shows that certain metabolites strongly correlate with microbial community structure and that some of these correlations are specific for the pre-diabetic state. Our study identifies novel relationships between the composition of the gutmicrobiota and circulating metabolites and provides a resource for future studies to understand host-gutmicrobiota relationships.

The vertebrate gutmicrobiota evolved in an environment typified by periodic fluctuations in nutrient availability, yet little is known about its responses to host feeding and fasting. As many model species (for example, mice) are adapted to lifestyles of frequent small meals, we turned to the Burmese python, a sit-and-wait foraging snake that consumes large prey at long intervals (>1 month), to examine the effects of a dynamic nutrient milieu on the gutmicrobiota. We used multiplexed 16S rRNA gene pyrosequencing to characterize bacterial communities harvested from the intestines of fasted and digesting snakes, and from their rodent meal. In this unprecedented survey of a reptilian host, we found that Bacteroidetes and Firmicutes numerically dominated the python gut. In the large intestine, fasting was associated with increased abundances of the genera Bacteroides, Rikenella, Synergistes and Akkermansia, and with reduced overall diversity. A marked postprandial shift in bacterial community configuration occurred. Between 12 h and 3 days after feeding, Firmicutes, including the taxa Clostridium, Lactobacillus and Peptostreptococcaceae, gradually outnumbered the fasting-dominant Bacteroidetes, and overall 'species'-level diversity increased significantly. Most lineages seemed to be indigenous to the python rather than ingested with the meal, but a dietary source of Lactobacillus could not be ruled out. Thus, the observed large-scale alterations of the gutmicrobiota that accompany the Burmese python's own dramatic physiological and morphological changes during feeding and fasting emphasize the need to consider both microbial and host cellular responses to nutrient flux. The Burmese python may provide a unique model for dissecting these interrelationships.

The human intestinal ecosystem, previously called the gut microflora is now known as the Human GutMicrobiota (HGM). Microbiome research has emphasized the potential role of this ecosystem in human homeostasis, offering unexpected opportunities in therapeutics, far beyond digestive diseases. It has also highlighted ethical, social and commercial concerns related to the gutmicrobiota. As diet factors are accepted to be the major regulator of the gutmicrobiota, the modulation of its composition, either by antibiotics or by food intake, should be regarded as a fascinating tool for improving the human health. Scientists, the food industry, consumers and policymakers alike are involved in this new field of nutrition. Defining how knowledge about the HGM is being translated into public perception has never been addressed before. This raises the question of metaphors associated with the HGM, and how they could be used to improve public understanding, and to influence individual decision-making on healthcare policy. This article suggests that a meeting of stakeholders from the social sciences, basic research and the food industry, taking an epistemological approach to the HGM, is needed to foster close, innovative partnerships that will help shape public perception and enable novel behavioural interventions that would benefit public health.

As the prevalence of obesity and associated disease continues to rise and concerns for the spiralling economic and social costs also escalate, innovative management strategies beyond primary prevention and traditional lifestyle interventions are urgently needed. The biological basis of disease is one avenue for further exploration in this context. Several key inflammatory markers have been consistently associated with both obesity and risk of adverse outcomes in obesity-associated diseases, which suggests that a persistent, low-grade, inflammatory response is a potentially modifiable risk factor. In this Review, we provide evidence supporting perturbation of the intestinal microbiota and changes in intestinal permeability as potential triggers of inflammation in obesity. Further characterisation of the mechanisms underpinning the triggers of such inflammatory responses in overweight and obese individuals could offer unique opportunities for intervention strategies to help ameliorate the risk of obesity-associated disease.

Full Text Available Introduction: Advances in tools for molecular investigations have allowed deeper understanding of how microbes can influence host physiology. A very interesting field of research that has gained attention recently is the possible role of gutmicrobiota in the development of obesity and metabolic disorders. Objective: The aim of this review is to discuss mechanisms that explain the influence of gutmicrobiota on host metabolism. Results and discussion: The gutmicrobiota is important for normal physiology of the host. However, differences in their composition may have different impacts on host metabolism. It has been shown that obese and lean subjects present different microbiota composition profile. These differences in microbiota composition may contribute to weight imbalance and impaired metabolism. The evidences from animal models suggest that it is possible that the microbiota of obese subjects has higher capacity to harvest energy from the diet providing substrates that can activate lipogenic pathways. In addition, microorganisms can also influence the activity of lipoprotein lipase interfering in the accumulation of triglycerides in the adipose tissue. The interaction of gutmicrobiota with the endocannabinoid system provides a route through which intestinal permeability can be altered. Increased intestinal permeability allows the entrance of endotoxins to the circulation, which are related to the induction of inflammation and insulin resistance in mice. The impact of the proposed mechanisms for humans still needs further investigations. However, the fact that gutmicrobiota can be modulated through dietary components highlights the importance to study how fatty acids, carbohydrates, micronutrients, prebiotics, and probiotics can influence gutmicrobiota composition and the management of obesity. Gutmicrobiota seems to be an important and promising target in the prevention and treatment of obesity and its related metabolic disturbances in

The mammalian gut is home to a diverse community of microbes. Advances in technology over the past two decades have allowed us to examine this community, the gutmicrobiota, in more detail, revealing a wide range of influences on host nutrition, health, and behavior. These host-gut microbe interactions appear to shape host plasticity and fitness in a variety of contexts, and therefore represent a key factor missing from existing models of human and non-human primate ecology and evolution. However, current studies of the gutmicrobiota tend to include limited contextual data or are clinical, making it difficult to directly test broad anthropological hypotheses. Here, I review what is known about the animal gutmicrobiota and provide examples of how gutmicrobiota research can be integrated into the study of human and non-human primate ecology and evolution with targeted data collection. Specifically, I examine how the gutmicrobiota may impact primate diet, energetics, disease resistance, and cognition. While gutmicrobiota research is proliferating rapidly, especially in the context of humans, there remain important gaps in our understanding of host-gut microbe interactions that will require an anthropological perspective to fill. Likewise, gutmicrobiota research will be an important tool for filling remaining gaps in anthropological research.

The development of the neonatal gut microbiome is influenced by multiple factors, such as delivery mode, feeding, medication use, hospital environment, early life stress, and genetics. The dysbiosis of gutmicrobiota persists during infancy, especially in high-risk preterm infants who experience lengthy stays in the Neonatal intensive care unit (NICU). Infant microbiome evolutionary trajectory is essentially parallel with the host (infant) neurodevelopmental process and growth. The role of the gut microbiome, the brain-gut signaling system, and its interaction with the host genetics have been shown to be related to both short and long term infant health and bio-behavioral development. The investigation of potential dysbiosis patterns in early childhood is still lacking and few studies have addressed this host-microbiome co-developmental process. Further research spanning a variety of fields of study is needed to focus on the mechanisms of brain-gut-microbiota signaling system and the dynamic host-microbial interaction in the regulation of health, stress and development in human newborns.

The development of the neonatal gut microbiome is influenced by multiple factors, such as delivery mode, feeding, medication use, hospital environment, early life stress, and genetics. The dysbiosis of gutmicrobiota persists during infancy, especially in high-risk preterm infants who experience lengthy stays in the Neonatal intensive care unit (NICU). Infant microbiome evolutionary trajectory is essentially parallel with the host (infant) neurodevelopmental process and growth. The role of the gut microbiome, the brain-gut signaling system, and its interaction with the host genetics have been shown to be related to both short and long term infant health and bio-behavioral development. The investigation of potential dysbiosis patterns in early childhood is still lacking and few studies have addressed this host-microbiome co-developmental process. Further research spanning a variety of fields of study is needed to focus on the mechanisms of brain-gut-microbiota signaling system and the dynamic host-microbial interaction in the regulation of health, stress and development in human newborns.

Obesity is a consequence of a complex interplay between the host genome and the prevalent obesogenic factors among the modern communities. The role of gutmicrobiota in the pathogenesis of the disorder was recently discovered; however, 16S-rRNA-based surveys revealed compelling but community-specific data. Considering this, despite unique diets, dietary habits and an uprising trend in obesity, the Indian counterparts are poorly studied. Here, we report a comparative analysis and quantification of dominant gutmicrobiota of lean, normal, obese and surgically treated obese individuals of Indian origin. Representative gut microbial diversity was assessed by sequencing fecal 16S rRNA libraries for each group (n=5) with a total of over 3000 sequences. We detected no evident trend in the distribution of the predominant bacterial phyla, Bacteroidetes and Firmicutes. At the genus level, the bacteria of genus Bacteroides were prominent among the obese individuals, which was further confirmed by qPCR ( > 0.05). In addition, a remarkably high archaeal density with elevated fecal SCFA levels was also noted in the obese group. On the contrary, the treated-obese individuals exhibited comparatively reduced Bacteroides and archaeal counts along with reduced fecal SCFAs. In conclusion, the study successfully identified a representative microbial diversity in the Indian subjects and demonstrated the prominence of certain bacterial groups in obese individuals; nevertheless, further studies are essential to understand their role in obesity.

The inflammatory intestinal disorder Crohn's disease (CD) has become a health challenge worldwide. The gutmicrobiota closely interacts with the host immune system, but its functional impact in CD is unclear. Except for studies on a small number of CD patients, analyses of the gutmicrobiota in CD...

The gutmicrobiota has been proposed as an environmental factor that promotes the progression of metabolic diseases. Here, we investigated how the gutmicrobiota modulates the global metabolic differences in duodenum, jejunum, ileum, colon, liver, and two white adipose tissue depots obtained from...

The gutmicrobiota influences many aspects of host metabolism. We have previously shown that the presence of a gutmicrobiota remodels lipid composition. Here we investigated how interaction between gutmicrobiota and dietary lipids regulates lipid composition in the liver and plasma, and gene expression in the liver. Germ-free and conventionally raised mice were fed a lard or fish oil diet for 11 weeks. We performed lipidomics analysis of the liver and serum and microarray analysis of the liver. As expected, most of the variation in the lipidomics dataset was induced by the diet, and abundance of most lipid classes differed between mice fed lard and fish oil. However, the gutmicrobiota also affected lipid composition. The gutmicrobiota increased hepatic levels of cholesterol and cholesteryl esters in mice fed lard, but not in mice fed fish oil. Serum levels of cholesterol and cholesteryl esters were not affected by the gutmicrobiota. Genes encoding enzymes involved in cholesterol biosynthesis were downregulated by the gutmicrobiota in mice fed lard and were expressed at a low level in mice fed fish oil independent of microbial status. In summary, we show that gutmicrobiota-induced regulation of hepatic cholesterol metabolism is dependent on dietary lipid composition.

An accumulating body of evidence shows that gutmicrobiota fulfill an important role in health and disease by modulating local and systemic immunity. The importance of the microbiome in the development of kidney disease, however, is largely unknown. To study this concept, we depleted gutmicrobiota

The intestinal tract of humans and animals is colonized by trillions of microorganisms that constitute a community or ecosystem known as the gutmicrobiota. The gutmicrobiota undergoes remarkable alterations during early age, reaches a relative stable state in adulthood, and is driven by internal

The interplay between both heredity and environmental factors seems to affect every stage of development from conception to the early postnatal period with potential long-term effects on child and adult health. During pregnancy, immune and metabolic functions of the fetus are dependent on the mother; moreover, the refinement of these functions seems to commence inside the uterus and to be diet sensitive. The microbiota inhabiting the intestinal tract develop an array of physiologic roles within the human body, which influences both metabolic and immune functions, particularly during early neonatal life and possibly even in utero. Transmission of bacteria from the mother to the neonate through direct contact with maternal microbiota during birth and through breast milk during lactation also seems to influence the infant's gut colonization, with potential health consequences. In this context, intentional modulation of microbiota composition through the use of probiotics during the perinatal and early postnatal period has been proposed as a possible dietary strategy to reduce risk of disease. Herein, studies are reviewed on the composition of the intestinal microbiota during pregnancy and clinical trials evaluating the effects of perinatal administration of probiotics on different clinical outcomes.

The intestinal microflora maintains a symbiotic relationship with the host under normal conditions, but its imbalance has recently been associated with several diseases. In chronic kidney disease (CKD), dysbiotic intestinal microflora has been reported with an increase in pathogenic flora compared to symbiotic flora. An enhanced permeability of the intestinal barrier, allowing the passage of endotoxins and other bacterial products to the blood, has also been shown in CKD. By fermenting undigested products that reach the colon, the intestinal microflora produce indoles, phenols and amines, among others, that are absorbed by the host, accumulate in CKD and have harmful effects on the body. These gut-derived uraemic toxins and the increased permeability of the intestinal barrier in CKD have been associated with increased inflammation and oxidative stress and have been involved in various CKD-related complications, including cardiovascular disease, anaemia, mineral metabolism disorders or the progression of CKD. The use of prebiotics, probiotics or synbiotics, among other approaches, could improve the dysbiosis and/or the increased permeability of the intestinal barrier in CKD. This article describes the situation of the intestinal microflora in CKD, the alteration of the intestinal barrier and its clinical consequences, the harmful effects of intestinal flora-derived uraemic toxins, and possible therapeutic options to improve this dysbiosis and reduce CKD-related complications.

Obesity is epidemic; chronic energy surplus is clearly important in obesity development but other factors are at play. Indigenous gutmicrobiota are implicated in the aetiopathogenesis of obesity and obesity-related disorders. Evidence from murine models initially suggested a role for the gutmicrobiota in weight regulation and the microbiota has been shown to contribute to the low grade inflammation that characterises obesity. The microbiota and its metabolites mediate some of the alterations of the microbiota-gut-brain axis, the endocannabinoid system, and bile acid metabolism, found in obesity-related disorders. Modulation of the gutmicrobiota is an attractive proposition for prevention or treatment of obesity, particularly as traditional measures have been sub-optimal.

Despite the accepted health benefits of consuming dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gutmicrobiota and alters disease risk. Using a gnotobiotic mouse model, in which animals were colonized with a synthetic human gutmicrobiota composed of fully sequenced commensal bacteria, we elucidated the functional interactions between dietary fiber, the gutmicrobiota, and the colonic mucus barrier, which serves as a primary defense against enteric pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gutmicrobiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation, together with a fiber-deprived, mucus-eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium. Our work reveals intricate pathways linking diet, the gut microbiome, and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics.

The first years of life are paramount in establishing our endogenous gutmicrobiota, which is strongly affected by diet and has repeatedly been linked with obesity. However, very few studies have addressed the influence of maternal obesity on infant gutmicrobiota, which may occur either through...... vertically transmitted microbes or through the dietary habits of the family. Additionally, very little is known about the effect of diet during the complementary feeding period, which is potentially important for gutmicrobiota development. Here, the gutmicrobiotas of two different cohorts of infants, born...... either of a random sample of healthy mothers (n = 114), or of obese mothers (n = 113), were profiled by 16S rRNA amplicon sequencing. Gutmicrobiota data were compared to breastfeeding patterns and detailed individual dietary recordings to assess effects of the complementary diet. We found that maternal...

ABSTRACT The formation of SCFA is the result of a complex interplay between diet and the gutmicrobiota within the gut lumen environment. The discovery of receptors, across a range of cell and tissue types for which short chain fatty acids SCFA appear to be the natural ligands, has led to increased interest in SCFA as signaling molecules between the gutmicrobiota and the host. SCFA represent the major carbon flux from the diet through the gutmicrobiota to the host and evidence is emerging f...

older siblings was associated with increased relative abundance of several bacterial taxa at both 9 and 18 months of age. Compared to the effect of having siblings, presence of household furred pets and early life infections had less pronounced effects on the gutmicrobiota. Gutmicrobiota...... of the hygiene hypothesis. However, no associations were found between gutmicrobiota and atopic symptoms of eczema and asthmatic bronchitis during early childhood and thus further studies are required to elucidate whether sibling-associated gut microbial changes influence development of allergies later...

The human gastrointestinal tract contains a highly complex ecosystem that harbors various microorganisms, which together create a unique environment within each individual. There is growing awareness that dietary habits are one of the essential factors contributing to the microbial diversity and community configuration that ultimately affects human health. From an evolutionary perspective, human dietary history can be viewed as a central factor in the selection of the gut microbial community and stabilization of the mutualistic host-microbial interaction, that together drive host phenotype. Herein, current knowledge concerning the influence of major dietary macrostructure and individual food ingredients is presented. This knowledge will provide perspectives for personalized gutmicrobiota management and, ultimately, movement toward an era of personalized nutrition and medicine.

The gutmicrobiota is involved in many aspects of host physiology but its role in body weight and glucose metabolism remains unclear. Here we studied the compositional changes of gutmicrobiota in diet-induced obesity mice that were conventionally raised or received microbiota transplantation. In conventional mice, the diversity of the faecal microbiota was weakly associated with 1st week weight gain but transferring the microbiota of mice with contrasting weight gain to germfree mice did not change obesity development or feed efficiency of recipients regardless whether the microbiota was taken before or after 10 weeks high fat (HF) feeding. Interestingly, HF-induced glucose intolerance was influenced by microbiota inoculation and improved glucose tolerance was associated with a low Firmicutes to Bacteroidetes ratio. Transplantation of Bacteroidetes rich microbiota compared to a control microbiota ameliorated glucose intolerance caused by HF feeding. Altogether, our results demonstrate that gutmicrobiota is involved in the regulation of glucose metabolism and the abundance of Bacteroidetes significantly modulates HF-induced glucose intolerance but has limited impact on obesity in mice. Our results suggest that gutmicrobiota is a part of complex aetiology of insulin resistance syndrome, individual microbiota composition may cause phenotypic variation associated with HF feeding in mice. PMID:27577172

Aims/hypothesis Recent studies indicate that an aberrant gutmicrobiota is associated with the development of type 1 diabetes, yet little is known about the microbiota in children who have diabetes at an early age. To this end, the microbiota of children aged 1–5 years with new-onset type 1 diabetes

Aims/hypothesis Recent studies indicate that an aberrant gutmicrobiota is associated with the development of type 1 diabetes, yet little is known about the microbiota in children who have diabetes at an early age. To this end, the microbiota of children aged 1-5 years with new-onset type 1 diabetes

The interaction between the gutmicrobiota and the host immune system is very important for balancing and resolving inflammation. The human microbiota begins to form during childbirth; the complex interaction between bacteria and host cells becomes critical for the formation of a healthy or a disease-promoting microbiota. C-section delivery, formula feeding, a high-sugar diet, a high-fat diet and excess hygiene negatively affect the health of the microbiota. Considering that the majority of the global population has experienced at least one of these factors that can lead to inflammatory disease, it is important to understand strategies to modulate the gutmicrobiota. In this review, we will discuss new insights into gutmicrobiota modulation as potential strategies to prevent and treat inflammatory diseases. Owing to the great advances in tools for microbial analysis, therapeutic strategies such as prebiotic, probiotic and postbiotic treatment and fecal microbiota transplantation have gained popularity. PMID:27757227

Human milk is a complete source of nourishment for the infant. Exclusive breastfeeding not only sustains the infant’s development but also guides the proliferation of a protective intestinal microbiota. Among the many components of milk that modulate the infant gutmicrobiota, the milk glycans, which comprise free oligosaccharides, glycoproteins, and glycolipids, are increasingly recognized as drivers of microbiota development and overall gut health. These glycans may display pleiotropic func...

To achieve these objectives, we will first develop a new humanized rat model harboring the gutmicrobiota from five-ten healthy normal human donors...fecal microbiota collected from normal healthy human donors will be used to inoculate pseudo germ-free (GF) Sprague Dawley (SD) rats to develop...AFRL-RH-WP-TR-2017-0001 Tailoring GutMicrobiota for Enhanced Resilience and Performance under Sleep-Deprived Conditions. Victor T. Chan

Full Text Available The gutmicrobiota refers to the trillions of microorganisms residing in the intestine and is integral in multiple physiological processes of the host. Recent research has shown that gut bacteria play a role in metabolic disorders such as obesity, diabetes, and cardiovascular diseases. The mechanisms by which the gutmicrobiota affects metabolic diseases are by two major routes: (1 the innate immune response to the structural components of bacteria (e.g., lipopolysaccharide resulting in inflammation and (2 bacterial metabolites of dietary compounds (e.g., SCFA from fiber, which have biological activities that regulate host functions. Gutmicrobiota has evolved with humans as a mutualistic partner, but dysbiosis in a form of altered gut metagenome and collected microbial activities, in combination with classic genetic and environmental factors, may promote the development of metabolic disorders. This paper reviews the available literature about the gutmicrobiota and aforementioned metabolic disorders and reveals the gaps in knowledge for future study.

The human gut contains a dense, complex and diverse microbial community, comprising the gut microbiome. Metagenomics has recently revealed the composition of genes in the gut microbiome, but provides no direct information about which genes are expressed or functioning. Therefore, our goal was to develop a novel approach to directly identify microbial proteins in fecal samples to gain information about the genes expressed and about key microbial functions in the human gut. We used a non-targeted, shotgun mass spectrometry-based whole community proteomics, or metaproteomics, approach for the first deep proteome measurements of thousands of proteins in human fecal samples, thus demonstrating this approach on the most complex sample type to date. The resulting metaproteomes had a skewed distribution relative to the metagenome, with more proteins for translation, energy production and carbohydrate metabolism when compared to what was earlier predicted from metagenomics. Human proteins, including antimicrobial peptides, were also identified, providing a non-targeted glimpse of the host response to the microbiota. Several unknown proteins represented previously undescribed microbial pathways or host immune responses, revealing a novel complex interplay between the human host and its associated microbes.

The human gut contains a dense, complex, and diverse microbial community, comprising the gut microbiome. Metagenomics has recently revealed the composition of genes in the gut microbiome, but provides no direct information about which genes are expressed or functioning. Therefore, our goal was to develop a novel approach to directly identify microbial proteins in fecal samples to gain information about what genes were expressed and about key microbial functions in the human gut. We used a non-targeted, shotgun mass spectrometry-based whole community proteomics, or metaproteomics, approach for the first deep proteome measurements of thousands of proteins in human fecal samples, thus demonstrating this approach on the most complex sample type to date. The resulting metaproteomes had a skewed distribution relative to the metagenome, with more proteins for translation, energy production, and carbohydrate metabolism compared to what was earlier predicted from metagenomics. Human proteins, including antimicrobial peptides, were also identified, providing a non-targeted glimpse of the host response to the microbiota. Several unknown proteins represented previously undescribed microbial pathways or host immune responses, revealing a novel complex interplay between the human host and its associated microbes.

Full Text Available The large and complex gutmicrobiota in animals has profound effects on feed utilization and metabolism. Currently, gastrointestinal diseases due to dysregulated gutmicrobiota are considered important factors that limit growth of the captive forest musk deer population. Compared with captive forest musk deer, wild forest musk deer have a wider feeding range with no dietary limitations, and their gutmicrobiota are in a relatively natural state. However, no reports have compared the gutmicrobiota between wild and captive forest musk deer. To gain insight into the composition of gutmicrobiota in forest musk deer under different food-source conditions, we employed high-throughput 16S rRNA sequencing technology to investigate differences in the gutmicrobiota occurring between captive and wild forest musk deer. Both captive and wild forest musk deer showed similar microbiota at the phylum level, which consisted mainly of Firmicutes and Bacteroidetes, although significant differences were found in their relative abundances between both groups. α-Diversity results showed that no significant differences occurred in the microbiota between both groups, while β-diversity results showed that significant differences did occur in their microbiota compositions. In summary, our results provide important information for improving feed preparation for captive forest musk deer and implementing projects where captive forest musk deer are released into the wild.

Summary Background An impaired gutmicrobiota has been reported as an important factor in the pathogenesis of obesity. Weight reduction has already been mentioned to improve gut microbial subpopulations involved in inflammatory processes, though other subpopulations still need further investigation. Thus, weight reduction in the context of a fasting program together with a probiotic intervention may improve the abundance and diversity of gutmicrobiota. Methods In this pilot study, overweight...

In the present world scenario, obesity has almost attained the level of a pandemic and is progressing at a rapid rate. This disease is the mother of all other metabolic disorders, which apart from placing an added financial burden on the concerned patient also has a negative impact on his/her well-being and health in the society. Among the various plausible factors for the development of obesity, the role of gutmicrobiota is very crucial. In general, the gut of an individual is inhabited by trillions of microbes that play a significant role in host energy homeostasis by their symbiotic interactions. Dysbiosis in gutmicrobiota causes disequilibrium in energy homeostasis that ultimately leads to obesity. Numerous mechanisms have been reported by which gutmicrobiota induces obesity in experimental models. However, which microbial community is directly linked to obesity is still unknown due to the complex nature of gutmicrobiota. Prebiotics and probiotics are the safer and effective dietary substances available, which can therapeutically alter the gutmicrobiota of the host. In this review, an effort was made to discuss the current mechanisms through which gutmicrobiota interacts with host energy metabolism in the context of obesity. Further, the therapeutic approaches (prebiotics/probiotics) that helped in positively altering the gutmicrobiota were discussed by taking experimental evidence from animal and human studies. In the closing statement, the challenges and future tasks within the field were discussed. PMID:28421057

Full Text Available In the present world scenario, obesity has almost attained the level of a pandemic and is progressing at a rapid rate. This disease is the mother of all other metabolic disorders, which apart from placing an added financial burden on the concerned patient also has a negative impact on his/her well-being and health in the society. Among the various plausible factors for the development of obesity, the role of gutmicrobiota is very crucial. In general, the gut of an individual is inhabited by trillions of microbes that play a significant role in host energy homeostasis by their symbiotic interactions. Dysbiosis in gutmicrobiota causes disequilibrium in energy homeostasis that ultimately leads to obesity. Numerous mechanisms have been reported by which gutmicrobiota induces obesity in experimental models. However, which microbial community is directly linked to obesity is still unknown due to the complex nature of gutmicrobiota. Prebiotics and probiotics are the safer and effective dietary substances available, which can therapeutically alter the gutmicrobiota of the host. In this review, an effort was made to discuss the current mechanisms through which gutmicrobiota interacts with host energy metabolism in the context of obesity. Further, the therapeutic approaches (prebiotics/probiotics that helped in positively altering the gutmicrobiota were discussed by taking experimental evidence from animal and human studies. In the closing statement, the challenges and future tasks within the field were discussed.

The prevalence of obesity, insulin resistance and type 2 diabetes has steadily increased in the last decades. In addition to the genetic and environmental factors, gutmicrobiota may play an important role in the modulation of intermediary phenotypes leading to metabolic disease. Obesity and type 2 diabetes are associated with specific changes in gutmicrobiota composition. The mechanisms underlying the association of specific gutmicrobiota and metabolic disease include increasing energy harvest from the diet, changes in host gene expression, energy expenditure and storage, and alterations in gut permeability leading to metabolic endotoxemia, inflammation and insulin resistance. In some studies, the modifications of gutmicrobiota induced by antibiotics, prebiotics and probiotics led to improved inflammatory activity in parallel to amelioration of insulin sensitivity and decreased adiposity. However, these effects were mainly observed in animal models. Their extrapolation to humans awaits further studies. The fascinating role of gutmicrobiota on metabolic disease opens new avenues in the treatment of obesity, insulin resistance and type 2 diabetes. A co-evolutionary clue for microbiota and insulin resistance is suggested.

The gutmicrobiota interacts with the host via neuroimmune, neuroendocrine and neural pathways. These pathways are components of the brain-gut-microbiota axis and preclinical evidence suggests that the microbiota can recruit this bidirectional communication system to modulate brain development, function and behaviour. The pathophysiology of depression involves neuroimmune-neuroendocrine dysregulation. However, the extent to which changes in gutmicrobiota composition and function mediate the dysregulation of these pathways is unknown. Thirty four patients with major depression and 33 matched healthy controls were recruited. Cytokines, CRP, Salivary Cortisol and plasma Lipopolysaccharide binding protein were determined by ELISA. Plasma tryptophan and kynurenine were determined by HPLC. Fecal samples were collected for 16s rRNA sequencing. A Fecal Microbiota transplantation was prepared from a sub group of depressed patients and controls and transferred by oral gavage to a microbiota-deficient rat model. We demonstrate that depression is associated with decreased gutmicrobiota richness and diversity. Fecal microbiota transplantation from depressed patients to microbiota-depleted rats can induce behavioural and physiological features characteristic of depression in the recipient animals, including anhedonia and anxiety-like behaviours, as well as alterations in tryptophan metabolism. This suggests that the gutmicrobiota may play a causal role in the development of features of depression and may provide a tractable target in the treatment and prevention of this disorder.

Full Text Available Birds represent a diverse and evolutionarily successful lineage, occupying a wide range of niches throughout the world. Like all vertebrates, avians harbour diverse communities of microorganisms within their guts, which collectively fulfil crucial roles in providing the host with nutrition and protection from pathogens. Across the field of avian microbiology knowledge is extremely uneven, with several species accounting for an overwhelming majority of all microbiological investigations. These include agriculturally important birds, such as chickens and turkeys, as well as birds of evolutionary or conservation interest. In our previous study we attempted the first meta-analysis of the avian gutmicrobiota, using 16S rRNA gene sequences obtained from a range of publicly available data sets. We have now extended our analysis to explore the microbiology of several key species in detail, to consider the avian microbiota within the context of what is known about other vertebrates, and to identify key areas of interest in avian microbiology for future study.

The intestinal microbiota is known to regulate host energy homeostasis and can be influenced by high-calorie diets. However, changes affecting the ecosystem at the functional level are still not well characterized. We measured shifts in cecal bacterial communities in mice fed a carbohydrate or high-fat (HF) diet for 12 weeks at the level of the following: (i) diversity and taxa distribution by high-throughput 16S ribosomal RNA gene sequencing; (ii) bulk and single-cell chemical composition by Fourier-transform infrared- (FT-IR) and Raman micro-spectroscopy and (iii) metaproteome and metabolome via high-resolution mass spectrometry. High-fat diet caused shifts in the diversity of dominant gut bacteria and altered the proportion of Ruminococcaceae (decrease) and Rikenellaceae (increase). FT-IR spectroscopy revealed that the impact of the diet on cecal chemical fingerprints is greater than the impact of microbiota composition. Diet-driven changes in biochemical fingerprints of members of the Bacteroidales and Lachnospiraceae were also observed at the level of single cells, indicating that there were distinct differences in cellular composition of dominant phylotypes under different diets. Metaproteome and metabolome analyses based on the occurrence of 1760 bacterial proteins and 86 annotated metabolites revealed distinct HF diet-specific profiles. Alteration of hormonal and anti-microbial networks, bile acid and bilirubin metabolism and shifts towards amino acid and simple sugars metabolism were observed. We conclude that a HF diet markedly affects the gut bacterial ecosystem at the functional level.

Cancers of the gastrointestinal (GI) tract continue to represent a major health problem, despite progress in therapy. Gutmicrobiota is a key element related to the genesis of GI cancers, countless papers addressing this burning issue across the world. We provide an updated knowledge of the involvement of gutmicrobiota in GI tumorigenesis, including its underlying mechanisms. We present also a comprehensive review of the evidence from animal and clinical studies using probiotics and/or prebiotics in the prevention and/or therapy of GI tumours, of GI cancer therapy-related toxicity and of post-operative complications. We summarize the anticarcinogenic mechanisms of these biotherapeutics from in vitro, animal and clinical interventions. More research is required to reveal the interactions of microflora with genetic, epigenetic and immunologic factors, diet and age, before any firm conclusion be drawn. Well-designed, randomized, double blind, placebo-controlled human studies using probiotics and/or prebiotics, with adequate follow-up are necessary in order to formulate directions for prevention and therapy.

Full Text Available Our gut harbors an extremely diverse collection of trillions of microbes that, besides degrading the complex dietary constituents, execute numerous activities vital for our metabolism and immune health. Although the importance of gutmicrobiota in maintaining digestive health has long been believed, its close correlation with numerous chronic ailments has recently been exposed, thanks to the innovative mechanistic studies on the compositional and functional aspects of gut microbial communities using germ-free or humanized animal models. Since a myriad of mysteries about the precise structures and functions of gut microbial communities in specific health situations still remains to be explicated, the emerging field of gutmicrobiota remains a foremost objective of research for microbiologists, computational biologists, clinicians, nutritionalists etc. Nevertheless, it is only after a comprehensive understanding of the structure, density and function of the gutmicrobiota that the new therapeutic targets could be captured and utilized for a healthier gut as well as overall wellbeing.

The gut-brain axis is a bi-directional integrated system composed by immune, endocrine, and neuronal components by which the gap between the gutmicrobiota and the brain is significantly impacted. An increasing number of different gut microbial species are now postulated to regulate brain function in health and disease. The westernized diet is hypothesized to be the cause of the current obesity levels in many countries, a major socio-economical health problem. Experimental and epidemiological evidence suggest that the gutmicrobiota is responsible for significant immunologic, neuronal, and endocrine changes that lead to obesity. We hypothesize that the gutmicrobiota, and changes associated with diet, affect the gut-brain axis and may possibly contribute to the development of mental illness. In this review, we discuss the links between diet, gut dysbiosis, obesity, and immunologic and neurologic diseases that impact brain function and behavior.

The gutmicrobiota plays important roles in proper gut function and can contribute to or help prevent disease. Whole grains, including oats, constitute important sources of nutrients for the gutmicrobiota and contribute to a healthy gut microbiome. In particular, whole grains provide NSP and resistant starch, unsaturated TAG and complex lipids, and phenolics. The composition of these constituents is unique in oats compared with other whole grains. Therefore, oats may contribute distinctive effects on gut health relative to other grains. Studies designed to determine these effects may uncover new human-health benefits of oat consumption.

Full Text Available The colonization and development of gutmicrobiota immediately after birth is highly variable and depends on several factors, such as delivery mode and modality of feeding during the first months of life. A cohort of 31 mother and neonate pairs, including 25 at-term caesarean (CS and 6 vaginally (V delivered neonates (DNs, were included in this study and 121 meconium/faecal samples were collected at days 1 through 30 following birth. Operational taxonomic units (OTUs were assessed in 69 stool samples by phylogenetic microarray HITChip and inter- and intra-individual distributions were established by inter-OTUs correlation matrices and OTUs co-occurrence or co-exclusion networks. 1H-NMR metabolites were determined in 70 stool samples, PCA analysis was performed on 55 CS DNs samples, and metabolome/OTUs co-correlations were assessed in 45 CS samples, providing an integrated map of the early microbiota OTUs-metabolome. A microbiota "core" of OTUs was identified that was independent of delivery mode and lactation stage, suggesting highly specialized communities that act as seminal colonizers of microbial networks. Correlations among OTUs, metabolites, and OTUs-metabolites revealed metabolic profiles associated with early microbial ecological dynamics, maturation of milk components, and host physiology.

The colonization and development of gutmicrobiota immediately after birth is highly variable and depends on several factors, such as delivery mode and modality of feeding during the first months of life. A cohort of 31 mother and neonate pairs, including 25 at-term caesarean (CS) and 6 vaginally (V) delivered neonates (DNs), were included in this study and 121 meconium/faecal samples were collected at days 1 through 30 following birth. Operational taxonomic units (OTUs) were assessed in 69 stool samples by phylogenetic microarray HITChip and inter- and intra-individual distributions were established by inter-OTUs correlation matrices and OTUs co-occurrence or co-exclusion networks. 1H-NMR metabolites were determined in 70 stool samples, PCA analysis was performed on 55 CS DNs samples, and metabolome/OTUs co-correlations were assessed in 45 CS samples, providing an integrated map of the early microbiota OTUs-metabolome. A microbiota “core” of OTUs was identified that was independent of delivery mode and lactation stage, suggesting highly specialized communities that act as seminal colonizers of microbial networks. Correlations among OTUs, metabolites, and OTUs-metabolites revealed metabolic profiles associated with early microbial ecological dynamics, maturation of milk components, and host physiology. PMID:26332837

Full Text Available An increasing number of human beings from developed countries are colonized by Escherichia coli strains producing colibactin, a genotoxin suspected to be associated with the development of colorectal cancers. Deoxynivalenol (DON is the most prevalent mycotoxin that contaminates staple food—especially cereal products—in Europe and North America. This study investigates the effect of the food contaminant DON on the genotoxicity of the E. coli strains producing colibactin. In vitro, intestinal epithelial cells were coexposed to DON and E. coli producing colibactin. In vivo, newborn rats colonized at birth with E. coli producing colibactin were fed a DON-contaminated diet. Intestinal DNA damage was estimated by the phosphorylation of histone H2AX. DON exacerbates the genotoxicity of the E. coli producing colibactin in a time- and dose-dependent manner in vitro. Although DON had no effect on the composition of the gutmicrobiota, and especially on the number of E. coli, a significant increase in DNA damage was observed in intestinal epithelial cells of animals colonized by E. coli strains producing colibactin and coexposed to DON compared to animals colonized with E. coli strains unable to produce colibactin or animals exposed only to DON. In conclusion, our data demonstrate that the genotoxicity of E. coli strains producing colibactin, increasingly present in the microbiota of asymptomatic human beings, is modulated by the presence of DON in the diet. This raises questions about the synergism between food contaminants and gutmicrobiota with regard to intestinal carcinogenesis.

ABSTRACT An increasing number of human beings from developed countries are colonized by Escherichia coli strains producing colibactin, a genotoxin suspected to be associated with the development of colorectal cancers. Deoxynivalenol (DON) is the most prevalent mycotoxin that contaminates staple food—especially cereal products—in Europe and North America. This study investigates the effect of the food contaminant DON on the genotoxicity of the E. coli strains producing colibactin. In vitro, intestinal epithelial cells were coexposed to DON and E. coli producing colibactin. In vivo, newborn rats colonized at birth with E. coli producing colibactin were fed a DON-contaminated diet. Intestinal DNA damage was estimated by the phosphorylation of histone H2AX. DON exacerbates the genotoxicity of the E. coli producing colibactin in a time- and dose-dependent manner in vitro. Although DON had no effect on the composition of the gutmicrobiota, and especially on the number of E. coli, a significant increase in DNA damage was observed in intestinal epithelial cells of animals colonized by E. coli strains producing colibactin and coexposed to DON compared to animals colonized with E. coli strains unable to produce colibactin or animals exposed only to DON. In conclusion, our data demonstrate that the genotoxicity of E. coli strains producing colibactin, increasingly present in the microbiota of asymptomatic human beings, is modulated by the presence of DON in the diet. This raises questions about the synergism between food contaminants and gutmicrobiota with regard to intestinal carcinogenesis. PMID:28292979

Acute cholecystitis (AC) is one of the most common surgical diseases. Bacterial infection accounts for 50% to 85% of the disease's onset. Since there is a close relationship between the biliary system and the gut, the aims of this study were to characterize and determine the influence of gutmicrobiota on AC, to detect the pathogenic microorganism in the biliary system, and to explore the relationship between the gut and bile microbiota of patients with AC. A total of 185 713 high-quality sequence reads were generated from the faecal samples of 15 patients and 13 healthy controls by 16S rRNA gene pyrosequencing. Patients' samples were significantly enriched in Akkermansia, Enterobacter and Escherichia/Shigella group. The healthy controls, however, showed significant enrichment of Clostridiales, Coprococcus, Coprobacillaceae, Paraprevotella, Turicibacter and TM7-3 in their faecal samples. Escherichia coli was the main biliary pathogenic microorganism, among others such as Klebsiella spp., Clostridium perfringens, Citrobacter freundii and Enterobacter cloacae in the bile of the patients. Additionally, the amount of bile endotoxin significantly correlated with the number of Enterobacteriaceae, especially E. coli. Our data indicate that Enterobacteriaceae might play essential role in the pathogenesis and/or progress of AC. This was verified in an in vivo model using a pathogenic E. coli isolated from one of the patients in guinea pigs and observed marked gallbladder inflammation and morphologic changes. This study thus provides insight which could be useful for the prevention, diagnosis and treatment of AC and related diseases by controlling the growth of Enterobacteriaceae to alleviate the infection.

Several studies point towards alteration in gutmicrobiota composition and function in coeliac disease, some of which can precede the onset of disease and/or persist when patients are on a gluten-free diet. Evidence also exists that the gutmicrobiota might promote or reduce coeliac-disease-associated immunopathology. However, additional studies are required in humans and in mice (using gnotobiotic technology) to determine cause–effect relationships and to identify agents for modulating the gutmicrobiota as a therapeutic or preventative approach for coeliac disease. In this Review, we summarize the current evidence for altered gutmicrobiota composition in coeliac disease and discuss how the interplay between host genetics, environmental factors and the intestinal microbiota might contribute to its pathogenesis. Moreover, we highlight the importance of utilizing animal models and long-term clinical studies to gain insight into the mechanisms through which host–microbial interactions can influence host responses to gluten. PMID:26055247

Full Text Available Bariatric surgery is highly successful in improving health compared to conventional dietary treatments. It has been suggested that the gutmicrobiota is a relevant factor in weight loss after bariatric surgery. Considering that bariatric procedures cause different rearrangements of the digestive tract, they probably have different effects on the gutmicrobiota. In this study, we compared the impact of medical treatment, sleeve gastrectomy and Roux-en-Y gastric bypass on the gutmicrobiota from obese subjects. Anthropometric and clinical parameters were registered before, 6 and 12 months after treatment. Fecal samples were collected and microbiota composition was studied before and six months post treatment using 16S rRNA gene sequencing and qPCR. In comparison to dietary treatment, changes in intestinal microbiota were more pronounced in patients subjected to surgery, observing a bloom in Proteobacteria. Interestingly, Bacteroidetes abundance was largely different after six months of each surgical procedure. Furthermore, changes in weight and BMI, or glucose metabolism, correlated positively with changes in these two phyla in these surgical procedures. These results indicate that distinct surgical procedures alter the gutmicrobiota differently, and changes in gutmicrobiota might contribute to health improvement. This study contributes to our understanding of the impact of weight loss surgery on the gutmicrobiota, and could be used to replicate this effect using targeted therapies.

Lifestyle habits, host gene repertoire, and alterations in the intestinal microbiota concur to the development of obesity. A great deal of research has recently been focused on investigating the role gutmicrobiota plays in the pathogenesis of metabolic dysfunctions and increased adiposity. Altered microbiota can affect host physiology through several pathways, including enhanced energy harvest, and perturbations in immunity, metabolic signaling, and inflammatory pathways. A broad range of "omics" technologies is now available to help decipher the interactions between the host and the gutmicrobiota at detailed genetic and functional levels. In particular, metabolomics--the comprehensive analysis of metabolite composition of biological fluids and tissues--could provide breakthrough insights into the links among the gutmicrobiota, host genetic repertoire, and diet during the development and progression of obesity. Here, we briefly review the most insightful findings on the involvement of gutmicrobiota in the pathogenesis of obesity. We also discuss how metabolomic approaches based on nuclear magnetic resonance spectroscopy could help understand the activity of gutmicrobiota in relation to obesity, and assess the effects of gutmicrobiota modulation in the treatment of this condition.

Full Text Available The gutmicrobiota plays a number of important roles including digestion, metabolism, extraction of nutrients, synthesis of vitamins, prevention against pathogen colonization, and modulation of the immune system. Alterations or changes in composition and biodiversity of the gutmicrobiota have been associated with many gastrointestinal tract (GIT disorders such as inflammatory bowel disease and colon cancer. Recent evidence suggests that altered composition and diversity of gutmicrobiota may play a role in the increased prevalence of metabolic diseases. This review article has two main objectives. First, it underscores approaches (such as probiotics, prebiotics, antimicrobial agents, bariatric surgery, and weight loss strategies and their prospects in modulating the gutmicrobiota in the management of metabolic diseases. Second, it highlights some of the current challenges and discusses areas of future research as it relates to the gutmicrobiota and metabolic diseases. The prospect of modulating the gutmicrobiota seems promising. However, considering that research investigating the role of gutmicrobiota in metabolic diseases is still in its infancy, more rigorous and well-designed in vitro, animal and clinical studies are needed.

The gutmicrobiota plays a number of important roles including digestion, metabolism, extraction of nutrients, synthesis of vitamins, prevention against pathogen colonization, and modulation of the immune system. Alterations or changes in composition and biodiversity of the gutmicrobiota have been associated with many gastrointestinal tract (GIT) disorders such as inflammatory bowel disease and colon cancer. Recent evidence suggests that altered composition and diversity of gutmicrobiota may play a role in the increased prevalence of metabolic diseases. This review article has two main objectives. First, it underscores approaches (such as probiotics, prebiotics, antimicrobial agents, bariatric surgery, and weight loss strategies) and their prospects in modulating the gutmicrobiota in the management of metabolic diseases. Second, it highlights some of the current challenges and discusses areas of future research as it relates to the gutmicrobiota and metabolic diseases. The prospect of modulating the gutmicrobiota seems promising. However, considering that research investigating the role of gutmicrobiota in metabolic diseases is still in its infancy, more rigorous and well-designed in vitro, animal and clinical studies are needed. PMID:24608927

The gutmicrobiota plays a number of important roles including digestion, metabolism, extraction of nutrients, synthesis of vitamins, prevention against pathogen colonization, and modulation of the immune system. Alterations or changes in composition and biodiversity of the gutmicrobiota have been associated with many gastrointestinal tract (GIT) disorders such as inflammatory bowel disease and colon cancer. Recent evidence suggests that altered composition and diversity of gutmicrobiota may play a role in the increased prevalence of metabolic diseases. This review article has two main objectives. First, it underscores approaches (such as probiotics, prebiotics, antimicrobial agents, bariatric surgery, and weight loss strategies) and their prospects in modulating the gutmicrobiota in the management of metabolic diseases. Second, it highlights some of the current challenges and discusses areas of future research as it relates to the gutmicrobiota and metabolic diseases. The prospect of modulating the gutmicrobiota seems promising. However, considering that research investigating the role of gutmicrobiota in metabolic diseases is still in its infancy, more rigorous and well-designed in vitro, animal and clinical studies are needed.

Gutmicrobiota have been implicated as a relevant factor in the development of type 2 diabetes mellitus (T2DM), and its diversity might be a cause of variation in animal models of T2DM. In this study, we aimed to characterise the gutmicrobiota of a T2DM mouse model with a long term vision of being able to target the gutmicrobiota to reduce the number of animals used in experiments. Male B6.V-Lep(ob)/J mice were characterized according to a number of characteristics related to T2DM, inflammation and gutmicrobiota. All findings were thereafter correlated to one another in a linear regression model. The total gutmicrobiota profile correlated to glycated haemoglobin, and high proportions of Prevotellaceae and Lachnospiraceae correlated to impaired or improved glucose intolerance, respectively. In addition, Akkermansia muciniphila disappeared with age as glucose intolerance worsened. A high proportion of regulatory T cells correlated to the gutmicrobiota and improved glucose tolerance. Furthermore, high levels of IL-10, IL-12 and TNF-α correlated to impaired glucose tolerance, blood glucose or glycated haemoglobin. The findings indicate that gutmicrobiota may contribute to variation in various disease read-outs in the B6.V-Lep(ob)/J model and considering them in both quality assurance and data evaluation for the B6.V-Lep(ob)/J model may have a reducing impact on the inter-individual variation.

Keratan sulfate (KS) represents an important family of glycosaminoglycans that are critical in diverse physiological processes. Recently, accumulating evidence has provided a wealth of information on the bioactivity of KS, which established it as an attractive candidate for drug development. However, although KS has been widely explored, less attention has been given to its effect on gutmicrobiota. Therefore, given that gutmicrobiota plays a pivotal role in health homeostasis and disease pathogenesis, we investigated here in detail the effect of KS on gutmicrobiota by high-throughput sequencing. As revealed by heatmap and principal component analysis, the mice gutmicrobiota was readily altered at different taxonomic levels by intake of low (8 mg/kg) and high dosage (40 mg/kg) of KS. Interestingly, KS exerted a differing effect on male and female microbiota. Specifically, KS induced a much more drastic increase in the abundance of Lactobacillus spp. in female (sixteen-fold) versus male mice (two-fold). In addition, combined with alterations in gutmicrobiota, KS also significantly reduced body weight while maintaining normal gut homeostasis. Altogether, we first demonstrated a sex-dependent effect of KS on gutmicrobiota and highlighted that it may be used as a novel prebiotic for disease management.

There is a growing realisation that the gut-brain axis and its regulation by the microbiota may play a key role in the biological and physiological basis of neurodevelopmental, age-related and neurodegenerative disorders. The routes of communication between the microbiota and brain are being unravelled and include the vagus nerve, gut hormone signalling, the immune system, tryptophan metabolism or by way of microbial metabolites such as short chain fatty acids. The importance of early life gutmicrobiota in shaping future health outcomes is also emerging. Disturbances of this composition by way of antibiotic exposure, lack of breastfeeding, infection, stress and the environmental influences coupled with the influence of host genetics can result in long-term effects on physiology and behaviour, at least in animal models. It is also worth noting that mode of delivery at birth influences microbiota composition with those born by Caesarean section having a distinctly different microbiota in early life to those born per vaginum. At the other extreme of life, ageing is associated with a narrowing in microbial diversity and healthy ageing correlates with a diverse microbiome. Recently, the gutmicrobiota has been implicated in a variety of conditions including depression, autism, schizophrenia and Parkinson's disease. There is still considerable debate as to whether or not the gutmicrobiota changes are core to the pathophysiology of such conditions or are merely epiphenomenal. It is plausible that such neuropsychiatric disorders might be treated in the future by targeting the microbiota either by microbiota transplantation, antibiotics or psychobiotics.

Full Text Available A close relationship exists between gutmicrobiota and immune responses. An imbalance of this relationship can determine local and systemic immune diseases. In fact the immune system plays an essential role in maintaining the homeostasis with the microbiota that normally resides in the gut, while, at the same time, the gutmicrobiota influences the immune system, modulating number and function of effector and regulatory T cells. To achieve this aim, mutual regulation between immune system and microbiota is achieved through several mechanisms, including the engagement of toll-like receptors (TLRs, pathogen-specific receptors expressed on numerous cell types. TLRs are able to recognize ligands from commensal or pathogen microbiota to maintain the tolerance or trigger the immune response. In this review, we summarize the latest evidences about the role of TLRs expressed in adaptive T cells, to understand how the immune system promotes intestinal homeostasis, fights invasion by pathogens, and is modulated by the intestinal microbiota.

obesity did not influence microbial diversity or specific taxon abundances during the complementary feeding period. Across cohorts, breastfeeding duration and composition of the complementary diet were found to be the major determinants of gutmicrobiota development. In both cohorts, gut microbial......The first years of life are paramount in establishing our endogenous gutmicrobiota, which is strongly affected by diet and has repeatedly been linked with obesity. However, very few studies have addressed the influence of maternal obesity on infant gutmicrobiota, which may occur either through...... either of a random sample of healthy mothers (n = 114), or of obese mothers (n = 113), were profiled by 16S rRNA amplicon sequencing. Gutmicrobiota data were compared to breastfeeding patterns and detailed individual dietary recordings to assess effects of the complementary diet. We found that maternal...

Overweight and obesity can currently be considered a major threat to human health and well-being. Recent scientific advances point to an aberrant compositional development of the gutmicrobiota and low-grade inflammation as contributing factors, in conjunction with excessive energy intake. A high-fat/energy diet alters the gutmicrobiota composition, which reciprocally engenders excessive energy harvesting and storage. Further, microbial imbalance increases gut permeability, leading to metabolic endotoxemia, inflammation and insulin resistance. Local intestinal immunologic homeostasis is achieved by tolerogenic immune responses to microbial antigens. In the context of amelioration of insulin sensitivity and decreased adiposity, the potential of gutmicrobiota modulation with specific probiotics and prebiotics lies in the normalization of aberrant microbiota, improved gut barrier function and creation of an anti-inflammatory milieu. This would suggest a role for probiotic/prebiotic interventions in the search for preventive and therapeutic applications in weight management.

Full Text Available The gutmicrobiota plays a crucial role in maintaining health. Alterations of the gut bacterial population have been associated with a number of diseases. Past and recent studies suggest that one can positively modify the contents of the gutmicrobiota by introducing prebiotics, probiotics, synbiotics, and other therapeutics. This paper focuses on probiotic modulation of the gutmicrobiota by their delivery to the lower gastrointestinal tract (GIT. There are numerous obstacles to overcome before microorganisms can be utilized as therapeutics. One important limitation is the delivery of viable cells to the lower GIT without a significant loss of cell viability and metabolic features through the harsh conditions of the upper GIT. Microencapsulation has been shown to overcome this, with various types of microcapsules available for resolving this limitation. This paper discusses the gutmicrobiota and its role in disease, with a focus on microencapsulated probiotics and their potentials and limitations.

There exists a bidirectional communication system between the gastrointestinal tract and the brain. Increasing evidence shows that gutmicrobiota can play a critical role in this communication; thus, the concept of a gutmicrobiota and brain axis is emerging. Here, we review recent findings in the relationship between intestinal microbes and brain function, such as anxiety, depression, stress, autism, learning, and memory. We highlight the advances in modulating brain development and behavior by probiotics, prebiotics, and diet through the gutmicrobiota-brain axis. A variety of mechanisms including immune, neural, and metabolic pathways may be involved in modulation of the gutmicrobiota-brain axis. We also discuss some future challenges. A deeper understanding of the relationship between the gut bacteria and their hosts is implicated in developing microbial-based therapeutic strategies for brain disorders.

The precise effects of HIV-1 on the gut microbiome are unclear. Initial cross-sectional studies provided contradictory associations between microbial richness and HIV serostatus and suggested shifts from Bacteroides to Prevotella predominance following HIV-1 infection, which have not been found in animal models or in studies matched for HIV-1 transmission groups. In two independent cohorts of HIV-1-infected subjects and HIV-1-negative controls in Barcelona (n = 156) and Stockholm (n = 84), men who have sex with men (MSM) predominantly belonged to the Prevotella-rich enterotype whereas most non-MSM subjects were enriched in Bacteroides, independently of HIV-1 status, and with only a limited contribution of diet effects. Moreover, MSM had a significantly richer and more diverse fecal microbiota than non-MSM individuals. After stratifying for sexual orientation, there was no solid evidence of an HIV-specific dysbiosis. However, HIV-1 infection remained consistently associated with reduced bacterial richness, the lowest bacterial richness being observed in subjects with a virological-immune discordant response to antiretroviral therapy. Our findings indicate that HIV gut microbiome studies must control for HIV risk factors and suggest interventions on gut bacterial richness as possible novel avenues to improve HIV-1-associated immune dysfunction.

Full Text Available The precise effects of HIV-1 on the gut microbiome are unclear. Initial cross-sectional studies provided contradictory associations between microbial richness and HIV serostatus and suggested shifts from Bacteroides to Prevotella predominance following HIV-1 infection, which have not been found in animal models or in studies matched for HIV-1 transmission groups. In two independent cohorts of HIV-1-infected subjects and HIV-1-negative controls in Barcelona (n = 156 and Stockholm (n = 84, men who have sex with men (MSM predominantly belonged to the Prevotella-rich enterotype whereas most non-MSM subjects were enriched in Bacteroides, independently of HIV-1 status, and with only a limited contribution of diet effects. Moreover, MSM had a significantly richer and more diverse fecal microbiota than non-MSM individuals. After stratifying for sexual orientation, there was no solid evidence of an HIV-specific dysbiosis. However, HIV-1 infection remained consistently associated with reduced bacterial richness, the lowest bacterial richness being observed in subjects with a virological-immune discordant response to antiretroviral therapy. Our findings indicate that HIV gut microbiome studies must control for HIV risk factors and suggest interventions on gut bacterial richness as possible novel avenues to improve HIV-1-associated immune dysfunction.

The precise effects of HIV-1 on the gut microbiome are unclear. Initial cross-sectional studies provided contradictory associations between microbial richness and HIV serostatus and suggested shifts from Bacteroides to Prevotella predominance following HIV-1 infection, which have not been found in animal models or in studies matched for HIV-1 transmission groups. In two independent cohorts of HIV-1-infected subjects and HIV-1-negative controls in Barcelona (n = 156) and Stockholm (n = 84), men who have sex with men (MSM) predominantly belonged to the Prevotella-rich enterotype whereas most non-MSM subjects were enriched in Bacteroides, independently of HIV-1 status, and with only a limited contribution of diet effects. Moreover, MSM had a significantly richer and more diverse fecal microbiota than non-MSM individuals. After stratifying for sexual orientation, there was no solid evidence of an HIV-specific dysbiosis. However, HIV-1 infection remained consistently associated with reduced bacterial richness, the lowest bacterial richness being observed in subjects with a virological-immune discordant response to antiretroviral therapy. Our findings indicate that HIV gut microbiome studies must control for HIV risk factors and suggest interventions on gut bacterial richness as possible novel avenues to improve HIV-1-associated immune dysfunction. PMID:27077120

Objective The consumption of an agrarian diet is associated with a reduced risk for many diseases associated with a ‘Westernised’ lifestyle. Studies suggest that diet affects the gutmicrobiota, which subsequently influences the metabolome, thereby connecting diet, microbiota and health. However, the degree to which diet influences the composition of the gutmicrobiota is controversial. Murine models and studies comparing the gutmicrobiota in humans residing in agrarian versus Western societies suggest that the influence is large. To separate global environmental influences from dietary influences, we characterised the gutmicrobiota and the host metabolome of individuals consuming an agrarian diet in Western society. Design and results Using 16S rRNA-tagged sequencing as well as plasma and urinary metabolomic platforms, we compared measures of dietary intake, gutmicrobiota composition and the plasma metabolome between healthy human vegans and omnivores, sampled in an urban USA environment. Plasma metabolome of vegans differed markedly from omnivores but the gutmicrobiota was surprisingly similar. Unlike prior studies of individuals living in agrarian societies, higher consumption of fermentable substrate in vegans was not associated with higher levels of faecal short chain fatty acids, a finding confirmed in a 10-day controlled feeding experiment. Similarly, the proportion of vegans capable of producing equol, a soy-based gutmicrobiota metabolite, was less than that was reported in Asian societies despite the high consumption of soy-based products. Conclusions Evidently, residence in globally distinct societies helps determine the composition of the gutmicrobiota that, in turn, influences the production of diet-dependent gut microbial metabolites. PMID:25431456

Recent studies have convincingly linked gutmicrobiota to traits relevant to atherosclerosis, such as insulin resistance, dyslipidemia and inflammation, and have revealed novel disease pathways involving microbe-derived metabolites. These results have important implications for understanding how environmental and genetic factors act together to influence cardiovascular disease (CVD) risk. Thus, dietary constituents are not only absorbed and metabolized by the host but they also perturb the gutmicrobiota, which in turn influence host metabolism and inflammation. It also appears that host genetics helps to shape the gutmicrobiota community. Here, we discuss challenges in understanding these interactions and the role they play in CVD.

an antibiotic treatment approach could be used instead. C57BL/6 mice were treated with ampicillin prior to inoculation at weaning or eight weeks of age with gutmicrobiota from lean or obese donors. The gutmicrobiota and clinical parameters of the recipients was characterized one and six weeks after...... of the donor phenotype were partly transmissible from obese to lean mice, in particularly beta cell hyperactivity in the obese recipients. Thus, a successful inoculation of gutmicrobiota was not age dependent in order for the microbes to colonize, and transferring different microbial compositions...

Recent studies have convincingly linked gutmicrobiota to traits relevant to atherosclerosis, such as insulin resistance, dyslipidemia and inflammation, and have revealed novel disease pathways involving microbe-derived metabolites. These results have important implications for understanding how environmental and genetic factors act together to influence cardiovascular disease (CVD) risk. Thus, dietary constituents are not only absorbed and metabolized by the host but they also perturb the gutmicrobiota, which in turn influence host metabolism and inflammation. It also appears that host genetics helps to shape the gutmicrobiota community. Here, we discuss challenges in understanding these interactions and the role they play in CVD. PMID:26071662

The first years of life are paramount in establishing our endogenous gutmicrobiota, which is strongly affected by diet and has repeatedly been linked with obesity. However, very few studies have addressed the influence of maternal obesity on infant gutmicrobiota, which may occur either through...... either of a random sample of healthy mothers (n = 114), or of obese mothers (n = 113), were profiled by 16S rRNA amplicon sequencing. Gutmicrobiota data were compared to breastfeeding patterns and detailed individual dietary recordings to assess effects of the complementary diet. We found that maternal...

Recent studies have revealed that the gutmicrobiota regulates many physiological functions, ranging from energy regulation and cognitive processes to toxin neutralization and immunity against pathogens. Accordingly, alterations in the composition of the gutmicrobiota have been shown to contribute to the development of various chronic diseases. The main objectives of this review are to present recent breakthroughs in the study of the gutmicrobiota and show that intestinal bacteria play a critical role in the development of different disease conditions, including obesity, fatty liver disease, and lung infection. We also highlight the potential application of prebiotics and probiotics in maintaining optimal health and treating chronic inflammatory and immunity-related diseases.

The first years of life are paramount in establishing our endogenous gutmicrobiota, which is strongly affected by diet and has repeatedly been linked with obesity. However, very few studies have addressed the influence of maternal obesity on infant gutmicrobiota, which may occur either through vertically transmitted microbes or through the dietary habits of the family. Additionally, very little is known about the effect of diet during the complementary feeding period, which is potentially important for gutmicrobiota development. Here, the gutmicrobiotas of two different cohorts of infants, born either of a random sample of healthy mothers (n = 114), or of obese mothers (n = 113), were profiled by 16S rRNA amplicon sequencing. Gutmicrobiota data were compared to breastfeeding patterns and detailed individual dietary recordings to assess effects of the complementary diet. We found that maternal obesity did not influence microbial diversity or specific taxon abundances during the complementary feeding period. Across cohorts, breastfeeding duration and composition of the complementary diet were found to be the major determinants of gutmicrobiota development. In both cohorts, gut microbial composition and alpha diversity were thus strongly affected by introduction of family foods with high protein and fiber contents. Specifically, intake of meats, cheeses, and Danish rye bread, rich in protein and fiber, were associated with increased alpha diversity. Our results reveal that the transition from early infant feeding to family foods is a major determinant for gutmicrobiota development. IMPORTANCE The potential influence of maternal obesity on infant gutmicrobiota may occur either through vertically transmitted microbes or through the dietary habits of the family. Recent studies have suggested that the heritability of obesity may partly be caused by the transmission of "obesogenic" gut microbes. However, the findings presented here suggest that maternal obesity per

The mammalian intestinal tract is heavily colonized with a dense, complex, and diversified microbial populations. In healthy individuals, an array of epithelial antimicrobial agents is secreted in the gut to aid intestinal homeostasis. Enterochromaffin cells (EC) in the intestinal epithelium are a major source of chromogranin A (CgA), which is a pro-hormone and can be cleaved into many bioactive peptides that include catestatin (CST). This study was carried out to evaluate the possible impact of CST on gutmicrobiota in vivo using a mouse model. The CST (Human CgA352−372) or normal saline was intrarectally administered in C57BL/6 male mice for 6 days and then sacrificed. Feces and colonic mucosa tissue samples were collected, DNA was extracted, the V4 region of bacterial 16S rRNA gene was amplified and subjected to MiSeq Illumina sequencing. The α-diversity was calculated using Chao 1 and β-diversity was determined using QIIME. Differences at the genus level were determined using partial least square discriminant analysis (PLS-DA). Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) was used to predict functional capacity of bacterial community. CST treatment did not modify bacterial richness in fecal and colonic mucosa-associated microbiota; however, treatment significantly modified bacterial community composition between the groups. Also, CST-treated mice had a significantly lower relative abundance of Firmicutes and higher abundance of Bacteroidetes, observed only in fecal samples. However, at lower phylogenetic levels, PLS-DA analysis revealed that some bacterial taxa were significantly associated with the CST-treated mice in both fecal and colonic mucosa samples. In addition, differences in predicted microbial functional pathways in both fecal and colonic mucosa samples were detected. The results support the hypothesis that CST treatment modulates gutmicrobiota composition under non-pathophysiological conditions

Background Recent evidence suggests that there is a link between metabolic diseases and bacterial populations in the gut. The aim of this study was to assess the differences between the composition of the intestinal microbiota in humans with type 2 diabetes and non-diabetic persons as control...... to control metabolic diseases by modifying the gutmicrobiota....... = 0.04). Conclusions The results of this study indicate that type 2 diabetes in humans is associated with compositional changes in intestinal microbiota. The level of glucose tolerance should be considered when linking microbiota with metabolic diseases such as obesity and developing strategies...

The beneficial roles of probiotics in lowering the gastrointestinal inflammation and preventing colorectal cancer have been frequently demonstrated, but their immunomodulatory effects and mechanism in suppressing the growth of extraintestinal tumors remain unexplored. Here, we adopted a mouse model and metagenome sequencing to investigate the efficacy of probiotic feeding in controlling s.c. hepatocellular carcinoma (HCC) and the underlying mechanism suppressing the tumor progression. Our result demonstrated that Prohep, a novel probiotic mixture, slows down the tumor growth significantly and reduces the tumor size and weight by 40% compared with the control. From a mechanistic point of view the down-regulated IL-17 cytokine and its major producer Th17 cells, whose levels decreased drastically, played critical roles in tumor reduction upon probiotics feeding. Cell staining illustrated that the reduced Th17 cells in the tumor of the probiotic-treated group is mainly caused by the reduced frequency of migratory Th17 cells from the intestine and peripheral blood. In addition, shotgun-metagenome sequencing revealed the crosstalk between gut microbial metabolites and the HCC development. Probiotics shifted the gut microbial community toward certain beneficial bacteria, including Prevotella and Oscillibacter, that are known producers of antiinflammatory metabolites, which subsequently reduced the Th17 polarization and promoted the differentiation of antiinflammatory Treg/Tr1 cells in the gut. Overall, our study offers novel insights into the mechanism by which probiotic treatment modulates the microbiota and influences the regulation of the T-cell differentiation in the gut, which in turn alters the level of the proinflammatory cytokines in the extraintestinal tumor microenvironment.

The beneficial roles of probiotics in lowering the gastrointestinal inflammation and preventing colorectal cancer have been frequently demonstrated, but their immunomodulatory effects and mechanism in suppressing the growth of extraintestinal tumors remain unexplored. Here, we adopted a mouse model and metagenome sequencing to investigate the efficacy of probiotic feeding in controlling s.c. hepatocellular carcinoma (HCC) and the underlying mechanism suppressing the tumor progression. Our result demonstrated that Prohep, a novel probiotic mixture, slows down the tumor growth significantly and reduces the tumor size and weight by 40% compared with the control. From a mechanistic point of view the down-regulated IL-17 cytokine and its major producer Th17 cells, whose levels decreased drastically, played critical roles in tumor reduction upon probiotics feeding. Cell staining illustrated that the reduced Th17 cells in the tumor of the probiotic-treated group is mainly caused by the reduced frequency of migratory Th17 cells from the intestine and peripheral blood. In addition, shotgun-metagenome sequencing revealed the crosstalk between gut microbial metabolites and the HCC development. Probiotics shifted the gut microbial community toward certain beneficial bacteria, including Prevotella and Oscillibacter, that are known producers of antiinflammatory metabolites, which subsequently reduced the Th17 polarization and promoted the differentiation of antiinflammatory Treg/Tr1 cells in the gut. Overall, our study offers novel insights into the mechanism by which probiotic treatment modulates the microbiota and influences the regulation of the T-cell differentiation in the gut, which in turn alters the level of the proinflammatory cytokines in the extraintestinal tumor microenvironment. PMID:26884164

The present report describes the presentations delivered at the 7th International Yakult Symposium, 'The Intestinal Microbiota and Probiotics: Exploiting Their Influence on Health', in London on 22-23 April 2013. The following two themes associated with health risks were covered: (1) the impact of age and diet on the gutmicrobiota and (2) the gutmicrobiota's interaction with the host. The strong influence of the maternal gutmicrobiota on neonatal colonisation was reported, as well as rapid changes in the gut microbiome of older people who move from community living to residential care. The effects of dietary changes on gut metabolism were described and the potential influence of inter-individual microbiota differences was noted, in particular the presence/absence of keystone species involved in butyrate metabolism. Several speakers highlighted the association between certain metabolic disorders and imbalanced or less diverse microbiota. Data from metagenomic analyses and novel techniques (including an ex vivo human mucosa model) provided new insights into the microbiota's influence on coeliac, obesity-related and inflammatory diseases, as well as the potential of probiotics. Akkermansia muciniphila and Faecalibacterium prausnitzii were suggested as targets for intervention. Host-microbiota interactions were explored in the context of gut barrier function, pathogenic bacteria recognition, and the ability of the immune system to induce either tolerogenic or inflammatory responses. There was speculation that the gutmicrobiota should be considered a separate organ, and whether analysis of an individual's microbiota could be useful in identifying their disease risk and/or therapy; however, more research is needed into specific diseases, different population groups and microbial interventions including probiotics.

The composition of the gutmicrobiota can vary widely between individual mice of the same batch and thereby affect the resulting outcome in experimental studies. Therefore, an efficient method is needed to equalize the gutmicrobiota prior to the start of critical experiments. In order to minimize variations in gutmicrobiota between animals and provide the animals with a Gram-negative flora exposing lipopolysaccharides in the cell-walls, C57BL/6 mice were given a mixture of ampicillin, metronidazole and clindamycin in the drinking water for 3 days and then Escherichia coli for two additional days. Treatment with antibiotics alone or with antibiotics in combination with E. coli was well tolerated by all animals. Body weight and liver weight were not affected, although higher hepatic fat content was found in treated animals (p gutmicrobiota was strongly reduced in animals treated with antibiotics and antibiotics in combination with E. coli (p microbiota between different treatment groups. The described treatment efficiently equalized the gutmicrobiota and provided the animals with a strong abundance of Enterobacteriaceae without changing the total load of bacteria. This is a straightforward, lenient and efficient method of pre-treatment to equalize the gutmicrobiota of mice as a starting procedure of animal studies.

Gastrointestinal pathogens must overcome many obstacles in order to successfully colonize a host, not the least of which is the presence of the gutmicrobiota, the trillions of commensal microorganisms inhabiting mammals' digestive tracts, and their products. It is well established that a healthy gutmicrobiota provides its host with protection from numerous pathogens, including Salmonella species, Clostridium difficile, diarrheagenic Escherichia coli, and Vibrio cholerae. Conversely, pathogenic bacteria have evolved mechanisms to establish an infection and thrive in the face of fierce competition from the microbiota for space and nutrients. Here, we review the evidence that gutmicrobiota-generated metabolites play a key role in determining the outcome of infection by bacterial pathogens. By consuming and transforming dietary and host-produced metabolites, as well as secreting primary and secondary metabolites of their own, the microbiota define the chemical environment of the gut and often determine specific host responses. Although most gutmicrobiota-produced metabolites are currently uncharacterized, several well-studied molecules made or modified by the microbiota are known to affect the growth and virulence of pathogens, including short-chain fatty acids, succinate, mucin O-glycans, molecular hydrogen, secondary bile acids, and the AI-2 quorum sensing autoinducer. We also discuss challenges and possible approaches to further study of the chemical interplay between microbiota and gastrointestinal pathogens.

Emerging evidence suggests an association between food sensitivity and gutmicrobiota in children with nephrotic syndrome. Diminished proteinuria resulted from eliminating cow's milk and the use of an oligoantigenic diet which excluded gluten, especially in patients with immune-related conditions, i.e., celiac disease and nephrotic syndrome. The mechanisms underlying the association of diet, gutmicrobiota, and dysregulation of the immune system are unknown. Gutmicrobiota is influenced by a number of factors including diet composition and other environmental epigenetic exposures. The imbalance in gutmicrobiota may be ameliorated by gluten-free and dairy-free diets. Gluten-free diet increased the number of unhealthy bacteria while reducing bacterial-induced cytokine production of IL-10. Thus, gluten-free diet may influence the composition and immune function of gutmicrobiota and should be considered a possible environmental factor associated with immune-related disease, including nephrotic syndrome. Furthermore, the imbalance of gutmicrobiota may be related to the development of cow's milk protein allergy. Investigations are needed to fill the gaps in our knowledge concerning the associations between the gut microbiome, environmental exposures, epigenetics, racial influences, and the propensity for immune dysregulation with its inherent risk to the developing individual.

Bidirectional signalling between the brain and the gastrointestinal tract is regulated at neural, hormonal, and immunological levels. Recent studies have shown that helminth infections can alter the normal gutmicrobiota. Studies have also shown that the gutmicrobiota is instrumental in the normal development, maturation and function of the brain. The pathophysiological pathways by which helminth infections contribute to altered cognitive function remain poorly understood. We put forward the hypothesis that gastrointestinal infections with parasitic worms, such as helminths, induce an imbalance of the gut-brain axis, which, in turn, can detrimentally manifest in brain development. Factors supporting this hypothesis are: 1) research focusing on intelligence and school performance in school-aged children has shown helminth infections to be associated with cognitive impairment, 2) disturbances in gutmicrobiota have been shown to be associated with important cognitive developmental effects, and 3) helminth infections have been shown to alter the gutmicrobiota structure. Evidence on the complex interactions between extrinsic (parasite) and intrinsic (host-derived) factors has been synthesised and discussed. While evidence in favour of the helminth-gutmicrobiota-central nervous system hypothesis is circumstantial, it would be unwise to rule it out as a possible mechanism by which gastrointestinal helminth infections induce childhood cognitive morbidity. Further empirical studies are necessary to test an indirect effect of helminth infections on the modulation of mood and behaviour through its effects on the gutmicrobiota.

Full Text Available Background: The gutmicrobiota plays an important role in human metabolism; previous studies suggest that the imbalance can cause a metabolic endotoxemia that may be linked to weight gain and insulin resistance. The purpose of this study was to investigate the relationship between the gutmicrobiota composition, the lipopolysaccharide levels and the metabolic profile in obese and normal-weight young subjects. Methods: We studied 32 obese (BMI ≥ 30 kg/m2 and 32 normal-weight subjects (BMI = 18.5-24.9 kg/m2, aged 18-25 years. Quantification of intestinal bacteria was performed by real-time PCR. Endotoxin units were determined with the test QCL-1000, and biochemical profile was performed under a standard protocol of Spinreact. Results: Obese individuals had a BMI of 34.5 (32.9-36.45 kg/m2, increased triglycerides (123 vs. 70 mg/dl, total cholesterol (168 vs. 142 mg/dl, and LDL-cholesterol (114 vs. 96.5 mg/dl. In obese subjects body temperature was higher than in normal-weight subjects. We found a greater number of Clostridum leptum and Lactobacillus (p Prevotella and Escherichia coli (p E. coli was associated with an increased risk of lipopolysaccharide levels ranging from 1 to 1.3 EU/ml. A positive correlation was found between serum lipopolysaccharides and BMI (r = 0.46, p = 0.008, triglyceride levels (r = 0.44, p = 0.011 as well as waist circumference (r = 0.34, p = 0.040, being more evident in young obese females. Conclusion: Subclinical metabolic endotoxemia determined by serum concentration of lipopolysaccharides was related to the smallest amount of E. coli, high triglyceride levels, and central adiposity in obese young persons.

Lactic acid bacteria were a dominant fraction of the intestinal microbiota in Arctic charr. Microbial based feeds were associated with similar changes in microbiota composition, but contrasting to the fish-meal based reference diet. Microbiota composition was similar in the proximal and distal gut, but dietary responses were specific to gut segment.

Crosstalk between organs is crucial for controlling numerous homeostatic systems (e.g. energy balance, glucose metabolism and immunity). Several pathological conditions, such as obesity and type 2 diabetes, are characterised by a loss of or excessive inter-organ communication that contributes to the development of disease. Recently, we and others have identified several mechanisms linking the gutmicrobiota with the development of obesity and associated disorders (e.g. insulin resistance, type 2 diabetes, hepatic steatosis). Among these, we described the concept of metabolic endotoxaemia (increase in plasma lipopolysaccharide levels) as one of the triggering factors leading to the development of metabolic inflammation and insulin resistance. Growing evidence suggests that gut microbes contribute to the onset of low-grade inflammation characterising these metabolic disorders via mechanisms associated with gut barrier dysfunctions. We have demonstrated that enteroendocrine cells (producing glucagon-like peptide-1, peptide YY and glucagon-like peptide-2) and the endocannabinoid system control gut permeability and metabolic endotoxaemia. Recently, we hypothesised that specific metabolic dysregulations occurring at the level of numerous organs (e.g. gut, adipose tissue, muscles, liver and brain) rely from gutmicrobiota modifications. In this review, we discuss the mechanisms linking gut permeability, adipose tissue metabolism, and glucose homeostasis, and recent findings that show interactions between the gutmicrobiota, the endocannabinoid system and the apelinergic system. These specific systems are discussed in the context of the gut-to-peripheral organ axis (intestine, adipose tissue and brain) and impacts on metabolic regulation. In the present review, we also briefly describe the impact of a variety of non-digestible nutrients (i.e. inulin-type fructans, arabinoxylans, chitin glucans and polyphenols). Their effects on the composition of the gutmicrobiota and

Animals have developed the means for supporting complex and dynamic consortia of microorganisms during their life cycle. A transcendent view of vertebrate biology therefore requires an understanding of the contributions of these indigenous microbial communities to host development and adult physiology. These contributions are most obvious in the gut, where studies of gnotobiotic mice have disclosed that the microbiota affects a wide range of biological processes, including nutrient processing and absorption, development of the mucosal immune system, angiogenesis, and epithelial renewal. The zebrafish (Danio rerio) provides an opportunity to investigate the molecular mechanisms underlying these interactions through genetic and chemical screens that take advantage of its transparency during larval and juvenile stages. Therefore, we developed methods for producing and rearing germ-free zebrafish through late juvenile stages. DNA microarray comparisons of gene expression in the digestive tracts of 6 days post fertilization germ-free, conventionalized, and conventionally raised zebrafish revealed 212 genes regulated by the microbiota, and 59 responses that are conserved in the mouse intestine, including those involved in stimulation of epithelial proliferation, promotion of nutrient metabolism, and innate immune responses. The microbial ecology of the digestive tracts of conventionally raised and conventionalized zebrafish was characterized by sequencing libraries of bacterial 16S rDNA amplicons. Colonization of germ-free zebrafish with individual members of its microbiota revealed the bacterial species specificity of selected host responses. Together, these studies establish gnotobiotic zebrafish as a useful model for dissecting the molecular foundations of host-microbial interactions in the vertebrate digestive tract. PMID:15070763

A wealth of information is emerging about the impact of gutmicrobiota on human health and diseases such as cardiovascular diseases, obesity and diabetes. As we learn more, we find out the gutmicrobiota has the potential as new territory for drug targeting. Some novel therapeutic approaches could be developed through reshaping the commensal microbial structure using combinations of different agents. The gutmicrobiota also affects drug metabolism, directly and indirectly, particularly towards the orally administered drugs. Herbal products have become the basis of traditional medicines such as traditional Chinese medicine and also been being considered valuable materials in modern drug discovery. Of note, low oral bioavailability but high bioactivity is a conundrum not yet solved for some herbs. Since most of herbal products are orally administered, the herbs' constituents are inevitably exposed to the intestinal microbiota and the interplays between herbal constituents and gutmicrobiota are expected. Emerging explorations of herb-microbiota interactions have an opportunity to revolutionize the way we view herbal therapeutics. The present review aims to provide information regarding the health promotion and/or disease prevention by the interplay between traditional herbs with low bioavailability and gutmicrobiota through gutmicrobiota via two different types of mechanisms: (1) influencing the composition of gutmicrobiota by herbs and (2) metabolic reactions of herbal constituents by gutmicrobiota. The major data bases (PubMed and Web of Science) were searched using "gutmicrobiota", "intestinal microbiota", "gut flora", "intestinal flora", "gut microflora", "intestinal microflora", "herb", "Chinese medicine", "traditional medicine", or "herbal medicine" as keywords to find out studies regarding herb-microbiota interactions. The Chinese Pharmacopoeia (2010 edition, Volume I) was also used to collect the data of commonly used medicinal herbs and their quality

We report the main characteristics of “Lachnoclostridium touaregense” strain Marseille-P2415T (= CSUR P2415 = DSM 102219), a new bacterial species isolated from the gutmicrobiota of a healthy young girl from Niger.

We report the main characteristics of ‘Lachnoclostridium massiliosenegalense’ strain mt23T (=CSUR P299 =DSM 102084), a new bacterial species isolated from the gutmicrobiota of a healthy young girl from Senegal.

Gutmicrobiota plays a key role in host physiology and metabolism. Indeed, the relevance of a well-balanced gutmicrobiota composition to an individual's health status is essential for the person's well-being. Currently, investigations are focused on analyzing the effects of pre- and probiotics as new therapeutic tools to counteract the disruption of intestinal bacterial balance occurring in several diseases. Polyphenols exert a wide range of beneficial health effects. However, although specific attention has been paid in recent years to the function of this "biological entity" in the metabolism of polyphenols, less is known about the modulatory capacity of these bioactive compounds on gutmicrobiota composition. This review provides an overview of the latest investigations carried out with pure polyphenols, extracts rich in polyphenols, and polyphenol-rich dietary sources (such as cocoa, tea, wine, soy products, and fruits) and critically discusses the consequences to gutmicrobiota composition which are produced.

Interpretation: American adults with allergies, especially to nuts and seasonal pollen, have low diversity, reduced Clostridiales, and increased Bacteroidales in their gutmicrobiota. This dysbiosis might be targeted to improve treatment or prevention of allergy.

The gutmicrobiota is a vast ensemble of microorganisms inhabiting the mammalian gastrointestinal tract that can impact physiologic and pathologic processes. However, our understanding of the underlying mechanism for the dynamic interaction between host and gutmicrobiota is still in its infancy. The highly evolved epigenetic modifications allow hosts to reprogram the genome in response to environmental stimuli, which may play a key role in triggering multiple human diseases. In spite of increasing studies in gutmicrobiota and epigenetic modifications, the correlation between them has not been well elaborated. Here, we review current knowledge of gutmicrobiota impacts on epigenetic modifications, the major evidence of which centers on DNA methylation and histone modification of the immune system.

Regular physical exercise provides many health benefits, protecting against the development of chronic diseases, and improving quality of life. Some of the mechanisms by which exercise provides these effects are the promotion of an anti-inflammatory state, reinforcement of the neuromuscular function, and activation of the hypothalamic–pituitary–adrenal (HPA) axis. Recently, it has been proposed that physical exercise is able to modify gutmicrobiota, and thus this could be another factor by which exercise promotes well-being, since gutmicrobiota appears to be closely related to health and disease. The purpose of this paper is to review the recent findings on gutmicrobiota modification by exercise, proposing several mechanisms by which physical exercise might cause changes in gutmicrobiota. PMID:26924990

Scope: Nutritional interventions based on the use of bioactive natural compounds might offer new possibilities for reshaping obesity-associated bacterial dysregulation or dysbiosis and improving health. We evaluated whether pterostilbene supplementation could induce changes in gutmicrobiota (GM) an...

Irritable bowel syndrome is a common functional gastrointestinal disorder and it is now evident that irritable bowel syndrome is a multi-factorial complex of changes in microbiota and immunology. The bidirectional neurohumoral integrated communication between the microbiota and the autonomous...... nervous system is called the gut-brain-axis, which integrates brain and GI functions, such as gut motility, appetite and weight. The gut-brain-axis has a central function in the perpetuation of irritable bowel syndrome and the microbiota plays a critical role. The purpose of this article is to review...... recent research concerning the epidemiology of irritable bowel syndrome, influence of microbiota, probiota, gut-brain-axis, and possible treatment modalities on irritable bowel syndrome....

There is growing appreciation for the importance of bacteria in shaping brain development and behaviour. Adolescence and early adulthood are crucial developmental periods during which exposure to harmful environmental factors can have a permanent impact on brain function. Such environmental factors include perturbations of the gut bacteria that may affect gut-brain communication, altering the trajectory of brain development, and increasing vulnerability to psychiatric disorders. Here we assess the effects of gut bacterial depletion from weaning onwards on adult cognitive, social and emotional behaviours and markers of gut-brain axis dysfunction in mice. Mice were treated with a combination of antibiotics from weaning onwards and effects on behaviours and potential gut-brain axis neuromodulators (tryptophan, monoamines, and neuropeptides) and BDNF expression were assessed in adulthood. Antibiotic-treatment depleted and restructured gutmicrobiota composition of caecal contents and decreased spleen weights in adulthood. Depletion of the gutmicrobiota from weaning onwards reduced anxiety, induced cognitive deficits, altered dynamics of the tryptophan metabolic pathway, and significantly reduced BDNF, oxytocin and vasopressin expression in the adult brain. Microbiota depletion from weaning onwards by means of chronic treatment with antibiotics in mice impacts on anxiety and cognitive behaviours as well as key neuromodulators of gut-brain communication in a manner that is similar to that reported in germ-free mice. This model may represent a more amenable alternative for germ-free mice in the assessment of microbiota modulation of behaviour. Finally, these data suggest that despite the presence of a normal gut microbiome in early postnatal life, reduced abundance and diversity of the gutmicrobiota from weaning influences adult behaviours and key neuromodulators of the microbiota-gut-brain axis suggesting that dysregulation of this axis in the post-weaning period may

Modern lifestyles, such as shift work, nocturnal social activities, and jet lag, disturb the circadian rhythm. The interaction between mammals and the co-evolved intestinal microbiota modulates host physiopathological processes. Radiotherapy is a cornerstone of modern management of malignancies; however, it was previously unknown whether circadian rhythm disorder impairs prognosis after radiotherapy. To investigate the effect of circadian rhythm on radiotherapy, C57BL/6 mice were housed in different dark/light cycles, and their intestinal bacterial compositions were compared using high throughput sequencing. The survival rate, body weight, and food intake of mice in diverse cohorts were measured following irradiation exposure. Finally, the enteric bacterial composition of irradiated mice that experienced different dark/light cycles was assessed using 16S RNA sequencing. Intriguingly, mice housed in aberrant light cycles harbored a reduction of observed intestinal bacterial species and shifts of gut bacterial composition compared with those of the mice kept under 12 h dark/12 h light cycles, resulting in a decrease of host radioresistance. Moreover, the alteration of enteric bacterial composition of mice in different groups was dissimilar. Our findings provide novel insights into the effects of biological clocks on the gut bacterial composition, and underpin that the circadian rhythm influences the prognosis of patients after radiotherapy in a preclinical setting.

Cooperative phenotypes are considered central to the functioning of microbial communities in many contexts, including communication via quorum sensing, biofilm formation, antibiotic resistance, and pathogenesis. The human intestine houses a dense and diverse microbial community critical to health, yet we know little about cooperation within this important ecosystem. Here we test experimentally for evolved cooperation within the Bacteroidales, the dominant Gram-negative bacteria of the human intestine. We show that during growth on certain dietary polysaccharides, the model member Bacteroides thetaiotaomicron exhibits only limited cooperation. Although this organism digests these polysaccharides extracellularly, mutants lacking this ability are outcompeted. In contrast, we discovered a dedicated cross-feeding enzyme system in the prominent gut symbiont Bacteroides ovatus, which digests polysaccharide at a cost to itself but at a benefit to another species. Using in vitro systems and gnotobiotic mouse colonization models, we find that extracellular digestion of inulin increases the fitness of B. ovatus owing to reciprocal benefits when it feeds other gut species such as Bacteroides vulgatus. This is a rare example of naturally-evolved cooperation between microbial species. Our study reveals both the complexity and importance of cooperative phenotypes within the mammalian intestinal microbiota.

Plasminogen-deficient (FVB/NPan-plg(tm1Jld), plg(tm1Jld)) mice, which are widely used as a wound-healing model, are prone to spontaneous rectal prolapses. The aims of this study were 1) to evaluate the fecal microbiome of plg(tm1Jld) mice for features that might contribute to the development of r...... the composition of the gutmicrobiota, and none of the clinical or biochemical parameters correlated with the gutmicrobiota composition....

purely genetic are involved in disease development. Here we review the influence of dietary and environmental factors on T1D development in humans as well as animal models. Even though data are still inconclusive, there are strong indications that gutmicrobiota dysbiosis plays an important role in T1D...... development and evidence from animal models suggests that gutmicrobiota manipulation might prove valuable in future prevention of T1D in genetically susceptible individuals....

Obesity and its associated disorders are a major public health concern. Although obesity has been mainly related with perturbations of the balance between food intake and energy expenditure, other factors must nevertheless be considered. Recent insight suggests that an altered composition and diversity of gutmicrobiota could play an important role in the development of metabolic disorders. This review discusses research aimed at understanding the role of gutmicrobiota in the pathogenesis of...

Background Bidirectional signalling between the brain and the gastrointestinal tract is regulated at neural, hormonal, and immunological levels. Recent studies have shown that helminth infections can alter the normal gutmicrobiota. Studies have also shown that the gutmicrobiota is instrumental in the normal development, maturation and function of the brain. The pathophysiological pathways by which helminth infections contribute to altered cognitive function remain poorly understood. Discuss...

What we understand about diabetes from decades of genetics research is now being supplemented with exciting new evidence based on a better understanding of how one of the biggest "environmental" factors the body is exposed to is influencing the pathogenesis of disease. The recent discovery that certain dietary nutrients possessing a trimethylamine (TMA) moiety (namely choline/phosphatidylcholine and L-carnitine) participate in the development of atherosclerotic heart disease has renewed attention towards the contributions of gutmicrobiota in the development of cardiovascular diseases. Collectively, animal and human studies reveal that conversion of these nutrient precursors to trimethylamine N-oxide (TMAO) depends on both microbial composition and host factors, and can be induced by dietary exposures. In addition, circulating TMAO levels are strongly linked to cardiovascular disease risks and various adverse cardio-renal consequences. Our group and others have further demonstrated that circulating TMAO levels are elevated in patients with type 2 diabetes mellitus compared to healthy controls and gutmicrobiota-dependent phosphatidylcholine metabolism has been implicated in metabolic dysregulation and insulin resistance in animal models. Therefore, preventive strategies to minimize adverse consequences associated with TMAO generation in the diabetic population are warranted.

Background Obesity induced by a high-caloric diet has previously been associated with changes in the gutmicrobiota in mice and in humans. In this study, pigs were cloned to minimize genetic and biological variation among the animals with the aim of developing a controlled metabolomic model...... suitable for a diet-intervention study. Cloning of pigs may be an attractive way to reduce genetic influences when investigating the effect of diet and obesity on different physiological sites. The aim of this study was to assess and compare the changes in the composition of the gutmicrobiota of cloned vs....... non-cloned pigs during development of obesity by a high-fat/high-caloric diet. Furthermore, we investigated the association between diet-induced obesity and the relative abundance of the phyla Firmicutes and Bacteroidetes in the fecal-microbiota. The fecal microbiota from obese cloned (n = 5) and non...

Gutmicrobiota influence the development and physiology of their animal hosts, and these effects are determined in part by the composition of these microbial communities. Gutmicrobiota composition can be affected by introduction of microbes from the environment, changes in the gut habitat during development, and acute dietary alterations. However, little is known about the relationship between gut and environmental microbiotas or about how host development and dietary differences during development impact the assembly of gutmicrobiota. We sought to explore these relationships using zebrafish, an ideal model because they are constantly immersed in a defined environment and can be fed the same diet for their entire lives. We conducted a cross-sectional study in zebrafish raised on a high-fat, control, or low-fat diet and used bacterial 16S rRNA gene sequencing to survey microbial communities in the gut and external environment at different developmental ages. Gut and environmental microbiota compositions rapidly diverged following the initiation of feeding and became increasingly different as zebrafish grew under conditions of a constant diet. Different dietary fat levels were associated with distinct gutmicrobiota compositions at different ages. In addition to alterations in individual bacterial taxa, we identified putative assemblages of bacterial lineages that covaried in abundance as a function of age, diet, and location. These results reveal dynamic relationships between dietary fat levels and the microbial communities residing in the intestine and the surrounding environment during ontogenesis. The ability of gutmicrobiota to influence host health is determined in part by their composition. However, little is known about the relationship between gut and environmental microbiotas or about how ontogenetic differences in dietary fat impact gutmicrobiota composition. We addressed these gaps in knowledge using zebrafish, an ideal model organism because their

Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gutmicrobiota is characterized by an overgrowth of potentially pathogenic bacteria (i.e., gram negative species) and a decrease in autochthonous familiae. Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences. We therefore described the features of the complex interaction between gutmicrobiota and cirrhotic host, the so called "gut-liver axis", with a particular attention to the acquired risk of bacterial translocation, systemic inflammation and the relationship with systemic infections in the cirrhotic patient. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis.

of this project was to investigate whether the aetiology to NNPD could be identified in the bacterial gut microbial changes. In order to be able to characterize the bacterial gutmicrobiota of numerous samples simultaneously the Gut Microbiotassay was developed. This is an assembly of 24 different primer sets...... targeting 16S or 23S rRNA genes of the major bacterial groups constituting the gutmicrobiota. This approach was applied due to the limited number of intestinal bacteria that currently can be cultivated. Primers were found in published literature, tested in silico and modified or designed if necessary...... of ileal and colonic contents of 50 control piglets and 52 case piglets from four Danish pig farms affected by NNPD were obtained and deeper taxonomic insight was acquired by sequencing the PCR amplicons. Statistic results from qPCR data revealed that the gutmicrobiota of NNPD-affected piglets differed...

The gutmicrobiota plays a crucial role in the bi-directional gut-brain axis, a communication that integrates the gut and central nervous system (CNS) activities. Animal studies reveal that gut bacteria influence behaviour, Brain-Derived Neurotrophic Factor (BDNF) levels and serotonin metabolism. In the present study, we report for the first time an analysis of the microbiota-gut-brain axis in zebrafish (Danio rerio). After 28 days of dietary administration with the probiotic Lactobacillus rhamnosus IMC 501, we found differences in shoaling behaviour, brain expression levels of bdnf and of genes involved in serotonin signalling/metabolism between control and treated zebrafish group. In addition, in microbiota we found a significant increase of Firmicutes and a trending reduction of Proteobacteria. This study demonstrates that selected microbes can be used to modulate endogenous neuroactive molecules in zebrafish.

Diet plays an important role in shaping the structure and function of the gutmicrobiota. The microbes and microbial products in turn can influence various aspects of host physiology. One promising route to affect host function and restore health is by altering the gut microbiome using dietary intervention. The individuality of the microbiome may pose a significant challenge, so we sought to determine how different microbiotas respond to the same dietary intervention in a controlled setting. We modeled gutmicrobiotas from three healthy donors in germfree mice and defined compositional and functional alteration following a change in dietary microbiota-accessible carbohydrates (MACs). The three gut communities exhibited responses that differed markedly in magnitude and in the composition of microbiota-derived metabolites. Adjustments in community membership did not correspond to the magnitude of changes in the microbial metabolites, highlighting potential challenges in predicting functional responses from compositional data and the need to assess multiple microbiota parameters following dietary interventions. IMPORTANCE Dietary modification has long been used empirically to modify symptoms in inflammatory bowel disease, irritable bowel syndrome, and a diverse group of diseases with gastrointestinal symptoms. There is both anecdotal and scientific evidence to suggest that individuals respond quite differently to similar dietary changes, and the highly individualized nature of the gutmicrobiota makes it a prime candidate for these differences. To overcome the typical confounding factors of human dietary interventions, here we employ ex-germfree mice colonized by microbiotas of three different humans to test how different microbiotas respond to a defined change in carbohydrate content of diet by measuring changes in microbiota composition and function using marker gene-based next-generation sequencing and metabolomics. Our findings suggest that the same diet has very

Although hibernating mammals wake occasionally to eat during torpor, this period represents a state of fasting. Fasting is known to alter the gutmicrobiota in nonhibernating mammals; therefore, hibernation may also affect the gutmicrobiota. However, there are few reports of gutmicrobiota in hibernating mammals. The present study aimed to compare the gutmicrobiota in hibernating torpid Syrian hamsters with that in active counterparts by using culture-independent analyses. Hamsters were allocated to either torpid, fed active, or fasted active groups. Hibernation was successfully induced by maintaining darkness at 4 degrees C. Flow cytometry analysis of cecal bacteria showed that 96-h fasting reduced the total gut bacteria. This period of fasting also reduced the concentrations of short chain fatty acids in the cecal contents. In contrast, total bacterial numbers and concentrations of short chain fatty acids were unaffected by hibernation. Denaturing gradient gel electrophoresis of PCR-amplified 16S rRNA gene fragments indicated that fasting and hibernation modulated the cecal microbiota. Analysis of 16S rRNA clone library and species-specific real-time quantitative PCR showed that the class Clostridia predominated in both active and torpid hamsters and that populations of Akkermansia muciniphila, a mucin degrader, were increased by fasting but not by hibernation. From these results, we conclude that the gutmicrobiota responds differently to fasting and hibernation in Syrian hamsters.

Autism spectrum disorder (ASD) is a series of neurodevelopmental disorders that are characterized by deficits in both social and cognitive functions. Although the exact etiology and pathology of ASD remain unclear, a disorder of the microbiota-gut-brain axis is emerging as a prominent factor in the generation of autistic behaviors. Clinical studies have shown that gastrointestinal symptoms and compositional changes in the gutmicrobiota frequently accompany cerebral disorders in patients with ASD. A disturbance in the gutmicrobiota, which is usually induced by a bacterial infection or chronic antibiotic exposure, has been implicated as a potential contributor to ASD. The bidirectional microbiota-gut-brain axis acts mainly through neuroendocrine, neuroimmune, and autonomic nervous mechanisms. Application of modulators of the microbiota-gut-brain axis, such as probiotics, helminthes and certain special diets, may be a promising strategy for the treatment of ASD. This review mainly discusses the salient observations of the disruptions of the microbiota-gut-brain axis in the pathogenesis of ASD and reveals its potential therapeutic role in autistic deficits.

It is suggested that gutmicrobiota play a role in the pathogenesis of obesity enhancing energy utilization from digested food. The influence of gutmicrobiota on resting energy expenditure (REE) has not been evaluated yet. The aim of the study is to assess the composition on gutmicrobiota and its association with REE in obese and normal weight subjects. REE measurement and semi-quantitative analysis of gutmicrobiota composition in aerobic and anaerobic conditions were performed in 50 obese and 30 normal weight subjects without concomitant diseases. A count of bacterial colony was greater in obese than in normal weight subjects. However, the proportion of Bacteroides spp. and Firmicutes was similar in both study groups. A positive correlation between REE (kcal/d) and total bacterial count (r = 0.26, p Bacteroides spp. and Firmicutes counts on REE. The composition of gutmicrobiota is not associated with the level of resting energy expenditure. The proportion of Bacteroides and Firmicutes in gutmicrobiota is not related to body mass.

Alterations of gut microbiome have been proposed to play a role in metabolic disease, but the major determinants of microbiota composition remain ill defined. Nutritional and sex hormone challenges, especially during early development, have been shown to permanently alter adult female phenotype and contribute to metabolic disturbances. In this study, we implemented large-scale microbiome analyses to fecal samples from groups of female rats sequentially subjected to various obesogenic manipulations, including sex hormone perturbations by means of neonatal androgenization or adult ovariectomy (OVX), as a model of menopause, to establish whether these phenomena are related to changes in gutmicrobiota. Basic metabolic profiles concerning glucose/insulin homeostasis were also explored. The effects of the sex hormonal perturbations, either developmentally (androgenization) or in adulthood (OVX), clearly outshone the impact of nutritional interventions, especially concerning the gutmicrobiota profile. Notably, we observed a lower diversity in the androgenized group, with the highest Firmicutes to Bacteroidetes ratio, supporting the occurrence of durable alterations in gutmicrobiota composition, even in adulthood. Moreover, the elimination of adult ovarian secretions by OVX affected the richness of gutmicrobiota. Our data are the first to document the durable impact of sex steroid manipulations, and particularly early androgenization, on gutmicrobiota composition. Such dysbiosis is likely to contribute to the metabolic perturbations of conditions of obesity linked to gonadal dysfunction in the female.

OBJECTIVE: Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota supports local mucosal immunity and is increasingly recognised as an important modulator of the systemic immune system. The precise role of the gutmicrobiota in bacterial pneumonia,

Background: Gut microbial diversity and abundance can profoundly impact human health. Research has shown that obese individuals are likely to have altered microbiota compared to lean individuals. Obesity is often considered a pro-inflammatory state, however the relationship between microbiota and i...

OBJECTIVE: Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota supports local mucosal immunity and is increasingly recognised as an important modulator of the systemic immune system. The precise role of the gutmicrobiota in bacterial pneumonia,

Males and females are known to have gender-specific differences in their immune system and gutmicrobiota composition. Whether these differences in gutmicrobiota composition are a cause or consequence of differences in the immune system is not known. To investigate this issue, gutmicrobiota from conventional males or females was transferred to germ-free (GF) animals of the same or opposing gender. We demonstrate that microbiota-independent gender differences in immunity are already present in GF mice. In particular, type I interferon signaling was enhanced in the intestine of GF females. Presumably, due to these immune differences bacterial groups, such as Alistipes, Rikenella, and Porphyromonadaceae, known to expand in the absence of innate immune defense mechanism were overrepresented in the male microbiota. The presence of these bacterial groups was associated with induction of weight loss, inflammation, and DNA damage upon transfer of the male microbiota to female GF recipients. In summary, our data suggest that microbiota-independent gender differences in the immune system select a gender-specific gutmicrobiota composition, which in turn further contributes to gender differences in the immune system. PMID:28713378

INTRODUCTION: Imbalance of the human gutmicrobiota in early childhood is suggested as a risk factor for immune-mediated disorders such as allergies. With the objective to modulate the intestinal microbiota, probiotic supplementation during infancy has been used for prevention of allergic diseases i

The gutmicrobiota composition of elderly hospitalized patients with Clostridium difficile infection (CDI) exposed to previous antibiotic treatment is still poorly investigated. The aim of this study was to compare the microbiota composition by means of 16S rRNA microbial profiling among three

The gutmicrobiota represents a metabolically active biomass of up to 2 kg in adult humans. Microbiota-derived molecules significantly contribute to the host metabolism. Large amounts of bacterial metabolites are taken up by the host and are subsequently utilized by the human body. For instance, sho

Full Text Available The human gutmicrobiota is impacted by host nutrition and health status and therefore represents a potentially adaptive phenotype influenced by metabolic and immune constraints. Previous studies contrasting rural populations in developing countries to urban industrialized ones have shown that industrialization is strongly correlated with patterns in human gutmicrobiota; however, we know little about the relative contribution of factors such as climate, diet, medicine, hygiene practices, host genetics, and parasitism. Here, we focus on fine-scale comparisons of African rural populations in order to (i contrast the gutmicrobiota of populations inhabiting similar environments but having different traditional subsistence modes and either shared or distinct genetic ancestry, and (ii examine the relationship between gut parasites and bacterial communities. Characterizing the fecal microbiota of Pygmy hunter-gatherers as well as Bantu individuals from both farming and fishing populations in Southwest Cameroon, we found that the gut parasite Entamoeba is significantly correlated with microbiome composition and diversity. We show that across populations, colonization by this protozoa can be predicted with 79% accuracy based on the composition of an individual's gutmicrobiota, and that several of the taxa most important for distinguishing Entamoeba absence or presence are signature taxa for autoimmune disorders. We also found gut communities to vary significantly with subsistence mode, notably with some taxa previously shown to be enriched in other hunter-gatherers groups (in Tanzania and Peru also discriminating hunter-gatherers from neighboring farming or fishing populations in Cameroon.

The human gutmicrobiota is impacted by host nutrition and health status and therefore represents a potentially adaptive phenotype influenced by metabolic and immune constraints. Previous studies contrasting rural populations in developing countries to urban industrialized ones have shown that industrialization is strongly correlated with patterns in human gutmicrobiota; however, we know little about the relative contribution of factors such as climate, diet, medicine, hygiene practices, host genetics, and parasitism. Here, we focus on fine-scale comparisons of African rural populations in order to (i) contrast the gutmicrobiota of populations inhabiting similar environments but having different traditional subsistence modes and either shared or distinct genetic ancestry, and (ii) examine the relationship between gut parasites and bacterial communities. Characterizing the fecal microbiota of Pygmy hunter-gatherers as well as Bantu individuals from both farming and fishing populations in Southwest Cameroon, we found that the gut parasite Entamoeba is significantly correlated with microbiome composition and diversity. We show that across populations, colonization by this protozoa can be predicted with 79% accuracy based on the composition of an individual's gutmicrobiota, and that several of the taxa most important for distinguishing Entamoeba absence or presence are signature taxa for autoimmune disorders. We also found gut communities to vary significantly with subsistence mode, notably with some taxa previously shown to be enriched in other hunter-gatherers groups (in Tanzania and Peru) also discriminating hunter-gatherers from neighboring farming or fishing populations in Cameroon.

Full Text Available Tacrolimus dosing to establish therapeutic levels in recipients of organ transplants is a challenging task because of much interpatient and intrapatient variability in drug absorption, metabolism, and disposition. In view of the reported impact of gut microbial species on drug metabolism, we investigated the relationship between the gutmicrobiota and tacrolimus dosing requirements in this pilot study of adult kidney transplant recipients. Serial fecal specimens were collected during the first month of transplantation from 19 kidney transplant recipients who either required a 50% increase from initial tacrolimus dosing during the first month of transplantation (Dose Escalation Group, n=5 or did not require such an increase (Dose Stable Group, n=14. We characterized bacterial composition in the fecal specimens by deep sequencing of the PCR amplified 16S rRNA V4-V5 region and we investigated the hypothesis that gut microbial composition is associated with tacrolimus dosing requirements. Initial tacrolimus dosing was similar in the Dose Escalation Group and in the Stable Group (4.2 ± 1.1 mg/day vs. 3.8 ± 0.8 mg/day, respectively, P=0.61, two-way between-group ANOVA using contrasts but became higher in the Dose Escalation Group than in the Dose Stable Group by the end of the first transplantation month (9.6 ± 2.4 mg/day vs. 3.3 ± 1.5 mg/day, respectively, P<0.001. Our systematic characterization of the gut microbial composition identified that fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was 11.8% in the Dose Escalation Group and 0.8% in the Dose Stable Group (P=0.002, Wilcoxon Rank Sum test, P<0.05 after Benjamini-Hochberg correction for multiple hypotheses. Fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was positively correlated with future tacrolimus dosing at 1 month (R=0.57, P=0.01 and had a coefficient ± standard error of 1.0 ± 0.6 (P=0.08 after multivariable linear

Nonalcoholic steatohepatitis (NASH) is characterized by the presence of steatosis, inflammation, and ballooning degeneration of hepatocytes, with or without fibrosis. The prevalence of NASH has increased with the obesity epidemic, but its etiology is multifactorial. The current studies suggest the role of gutmicrobiota in the development and progression of NASH. The aim is to review the studies that investigate the relationship between gutmicrobiota and NASH. These review also discusses the pathophysiological mechanisms and the influence of diet on the gut-liver axis. The available literature has proposed mechanisms for an association between gutmicrobiota and NASH, such as: modification energy homeostasis, lipopolysaccharides (LPS)-endotoxemia, increased endogenous production of ethanol, and alteration in the metabolism of bile acid and choline. There is evidence to suggest that NASH patients have a higher prevalence of bacterial overgrowth in the small intestine and changes in the composition of the gutmicrobiota. However, there is still a controversy regarding the microbiome profile in this population. The abundance of Bacteroidetes phylum may be increased, decreased, or unaltered in NASH patients. There is an increase in the Escherichia and Bacteroides genus. There is depletion of certain taxa, such as Prevotella and Faecalibacterium. Although few studies have evaluated the composition of the gutmicrobiota in patients with NASH, it is observed that these individuals have a distinct gutmicrobiota, compared to the control groups, which explains, at least in part, the genesis and progression of the disease through multiple mechanisms. Modulation of the gutmicrobiota through diet control offers new challenges for future studies.

The importance of the gut microbiome in determining not only overall health, but also in the metabolism of drugs and xenobiotics, is rapidly emerging. It is becoming increasingly clear that the gutmicrobiota can act in concert with the host cells to maintain intestinal homeostasis, cometabolize drugs and xenobiotics, and alter the expression levels of drug-metabolizing enzymes and transporters and the expression and activity levels of nuclear receptors. In this myriad of activities, the impact of the microbiota may be beneficial or detrimental to the host. Given that the interplay between the gutmicrobiota and host cells is likely subject to high interindividual variability, this work has tremendous implications for our ability to predict accurately a particular drug’s pharmacokinetics and a given patient population’s response to drugs. In this issue of Drug Metabolism and Disposition, a series of articles is presented that illustrate the progress and challenges that lie ahead as we unravel the intricacies associated with drug and xenobiotic metabolism by the gutmicrobiota. These articles highlight the underlying mechanisms that are involved and the use of in vivo and in vitro approaches that are currently available for elucidating the role of the gutmicrobiota in drug and xenobiotic metabolism. These articles also shed light on exciting new avenues of research that may be pursued as we consider the role of the gutmicrobiota as an endocrine organ, a component of the brain-gut axis, and whether the gutmicrobiota is an appropriate and amenable target for new drugs. PMID:26261284

The gut is the most extensively studied niche of the human microbiome. The aim of this study was to characterise the initial gutmicrobiota development of a cohort of breastfed infants (n = 192﻿) from 1 to 24 weeks of age.

To date, the majority of research into the human gutmicrobiota has focused on the bacterial fraction of the community. Inevitably, this has resulted in a poor understanding of the diversity and functionality of other intestinal microorganisms in the human gut. One such nonbacterial member is the mi

Aim. Evaluation of the impact of gut microflora on the pathophysiology of MS. Results. The etiopathogenesis of MS is not fully known. Gutmicrobiota may be of a great importance in the pathogenesis of MS, since recent findings suggest that substitutions of certain microbial population in the gut can lead to proinflammatory state, which can lead to MS in humans. In contrast, other commensal bacteria and their antigenic products may protect against inflammation within the central nervous system. The type of intestinal flora is affected by antibiotics, stress, or diet. The effects on MS through the intestinal microflora can also be achieved by antibiotic therapy and Lactobacillus. EAE, as an animal model of MS, indicates a strong influence of the gutmicrobiota on the immune system and shows that disturbances in gut physiology may contribute to the development of MS. Conclusions. The relationship between the central nervous system, the immune system, and the gutmicrobiota relates to the influence of microorganisms in the development of MS. A possible interaction between gutmicrobiota and the immune system can be perceived through regulation by the endocannabinoid system. It may offer an opportunity to understand the interaction comprised in the gut-immune-brain axis. PMID:28316999

Background The swine gutmicrobiota encompasses a large and diverse population of bacteria that play a significant role in pig health. As such, a number of recent studies have utilized high-throughput sequencing of the 16S rRNA gene to characterize the composition and structure of the swine gut micr...

and hormone system, to the brain (the gut-brain axis) and to host metabolism, as well as other functions of the host. This microbe-host communication is essential to maintain vital functions of the healthy host. Recently, however, the gutmicrobiota has been associated with a number of diseases, ranging from...

Full Text Available Obesity and its associated disorders are a major public health concern. Although obesity has been mainly related with perturbations of the balance between food intake and energy expenditure, other factors must nevertheless be considered. Recent insight suggests that an altered composition and diversity of gutmicrobiota could play an important role in the development of metabolic disorders. This review discusses research aimed at understanding the role of gutmicrobiota in the pathogenesis of obesity and type 2 diabetes mellitus. The establishment of gutmicrobiota is dependent on the type of birth. With effect from this point, gutmicrobiota remain quite stable, although changes take place between birth and adulthood due to external influences, such as diet, disease and environment. Understand these changes is important to predict diseases and develop therapies. A new theory suggests that gutmicrobiota contribute to the regulation of energy homeostasis, provoking the development of an impairment in energy homeostasis and causing metabolic diseases, such as insulin resistance or type 2 diabetes mellitus. The metabolic endotoxemia, modifications in the secretion of incretins and butyrate production might explain the influence of the microbiota in these diseases.

The gutmicrobiota provides essential signals for the development and appropriate function of the immune system. Through this critical contribution to immune fitness, the gutmicrobiota has a key role in health and disease. Recent advances in the technological applications to study microbial communities and their functions have contributed to a rapid increase in host–microbiota research. Although it still remains difficult to define a so-called ‘normal' or ‘healthy' microbial composition, alterations in the gutmicrobiota have been shown to influence the susceptibility of the host to different diseases. Current translational research combined with recent technological and computational advances have enabled in-depth study of the link between microbial composition and immune function, addressing the interplay between the gutmicrobiota and immune responses. As such, beneficial modulation of the gutmicrobiota is a promising clinical target for many prevalent diseases including inflammatory bowel disease, metabolic abnormalities such as obesity, reduced insulin sensitivity and low-grade inflammation, allergy and protective immunity against infections.

Full Text Available Early weaned piglets are vulnerable to diarrhea because of weaning stress and immaturity of intestinal tract. Compelling evidence suggests that gutmicrobiota is vital to host health. However, it is not well understood on the composition and succession of piglet gutmicrobiota during the weaning transition. In our two trials, total 17 commercial piglets were studied in a pig farm in Jiangxi Province, China. Fresh feces were collected for four times (10 days before weaned, weaned day, 10 days after weaned, 21 days after weaned by rectal massage. Fecal bacterial composition was assessed by 16S rRNA gene V3–V4 regions sequencing by Illumina Miseq platform. The results showed that the gutmicrobiota of piglets shifted quickly after weaned and reached relatively stable level in 10 days after weaned. The alpha diversity increased significantly with the age of piglets. The microbiota of suckling piglets was mainly represented by Fusobacterium, Lactobacillus, Bacteroides, Escherichia/Shigella, and Megasphaera. This pattern contrasted with that of Clostridium sensu stricto, Roseburia, Paraprevotella, Clostridium XIVa, and Blautia, which were major representative genera after weaned. In summary, we delineated the development of piglet gutmicrobiota during the weaning transition. This study helps us understand the maturing development of gutmicrobiota in commercial piglets.

Obesity and its associated disorders are a major public health concern. Although obesity has been mainly related with perturbations of the balance between food intake and energy expenditure, other factors must nevertheless be considered. Recent insight suggests that an altered composition and diversity of gutmicrobiota could play an important role in the development of metabolic disorders. This review discusses research aimed at understanding the role of gutmicrobiota in the pathogenesis of obesity and type 2 diabetes mellitus (TDM2). The establishment of gutmicrobiota is dependent on the type of birth. With effect from this point, gutmicrobiota remain quite stable, although changes take place between birth and adulthood due to external influences, such as diet, disease and environment. Understand these changes is important to predict diseases and develop therapies. A new theory suggests that gutmicrobiota contribute to the regulation of energy homeostasis, provoking the development of an impairment in energy homeostasis and causing metabolic diseases, such as insulin resistance or TDM2. The metabolic endotoxemia, modifications in the secretion of incretins and butyrate production might explain the influence of the microbiota in these diseases.

Islet autoimmunity in children who later progress to type 1 diabetes is preceded by dysregulated serum metabolite profiles, but the origin of these metabolic changes is unknown. The gutmicrobiota affects host metabolism and changes in its composition contribute to several immune-mediated diseases; however, it is not known whether the gutmicrobiota is involved in the early metabolic disturbances in progression to type 1 diabetes. We rederived non-obese diabetic (NOD) mice as germ free to explore the potential role of the gutmicrobiota in the development of diabetic autoimmunity and to directly investigate whether the metabolic profiles associated with the development of type 1 diabetes can be modulated by the gutmicrobiota. The absence of a gutmicrobiota in NOD mice did not affect the overall diabetes incidence but resulted in increased insulitis and levels of interferon gamma and interleukin 12; these changes were counterbalanced by improved peripheral glucose metabolism. Furthermore, we observed a markedly increased variation in blood glucose levels in the absence of a microbiota in NOD mice that did not progress to diabetes. Additionally, germ-free NOD mice had a metabolite profile similar to that of pre-diabetic children. Our data suggest that germ-free NOD mice have reduced glycaemic control and dysregulated immunologic and metabolic responses.

Carrageenan, agarose, and alginate are algae-derived undigested polysaccharides that have been used as food additives for hundreds of years. Fermentation of dietary carbohydrates of our food in the lower gut of humans is a critical process for the function and integrity of both the bacterial community and host cells. However, little is known about the fermentation of these three kinds of seaweed carbohydrates by human gutmicrobiota. Here, the degradation characteristics of carrageenan, agarose, alginate, and their oligosaccharides, by Bacteroides xylanisolvens, Bacteroides ovatus, and Bacteroides uniforms, isolated from human gutmicrobiota, are studied.

Obesity is increasing worldwide at an alarming rate which has reached epidemic proportions. Obesity and its co‐morbidities such as cardiovascular disease, type‐2 diabetes and cancer are of great economical burden to the countries affected. Efforts have been made to identify the causal factors...... that lead to obesity and maintenance of the obese state. Recently the gutmicrobiota has been implicated of being a contributing factor to obesity. Therefore the gutmicrobiota is a potential target for management of obesity and its co‐associated morbidities by changing the composition of the microbiota...... by pre‐ and probiotics diet supplements. In order to investigate the impact of diet and obesity on gutmicrobiota and vice versa in humans, there is a need for translational animal models that can contribute to the understanding of obesity and its related diseases. Pigs are often used in intervention...

Human milk is a complete source of nourishment for the infant. Exclusive breastfeeding not only sustains the infant's development but also guides the proliferation of a protective intestinal microbiota. Among the many components of milk that modulate the infant gutmicrobiota, the milk glycans, which comprise free oligosaccharides, glycoproteins, and glycolipids, are increasingly recognized as drivers of microbiota development and overall gut health. These glycans may display pleiotropic functions, conferring protection against infectious diseases and also acting as prebiotics, selecting for the growth of beneficial intestinal bacteria. The prebiotic effect of milk glycans has direct application to prevention of diseases such as necrotizing enterocolitis, a common and devastating disease of preterm infants. In this article, we review the impact of the human (and bovine) milk glycome on gut health through establishment of a milk-oriented microbiota in the neonate.

The healthy intestine represents a remarkable interface where sterile host tissues come in contact with gutmicrobiota, in a balanced state of homeostasis. The imbalance of gut homeostasis is associated with the onset of many severe pathological conditions, such as inflammatory bowel disease (IBD), a chronic gastrointestinal disorder increasing in incidence and severely influencing affected individuals. Despite the recent development of next generation sequencing and bioinformatics, the current scientific knowledge of specific triggers and diagnostic markers to improve interventional approaches in IBD is still scarce. In this review we present and discuss currently available and emerging therapeutic options in modulating composition and metabolic activity of gutmicrobiota in patients affected by IBD. Therapeutic approaches at the microbiota level, such as dietary interventions alone or with probiotics, prebiotics and synbiotics, administration of antibiotics, performing fecal microbiota transplantation (FMT) and the use of nematodes, all represent a promising opportunities towards establishing and maintaining of well-being as well as improving underlying IBD symptoms.

Traditionally bacteria have been considered as either pathogens, commensals or symbionts. The mammal gut harbors 10(14) organisms dispersed on approximately 1000 different species. Today, diagnostics, in contrast to previous cultivation techniques, allow the identification of close to 100% of bacterial species. This has revealed that a range of animal models within different research areas, such as diabetes, obesity, cancer, allergy, behavior and colitis, are affected by their gutmicrobiota. Correlation studies may for some diseases show correlation between gutmicrobiota composition and disease parameters higher than 70%. Some disease phenotypes may be transferred when recolonizing germ free mice. The mechanistic aspects are not clear, but some examples on how gut bacteria stimulate receptors, metabolism, and immune responses are discussed. A more deeper understanding of the impact of microbiota has its origin in the overall composition of the microbiota and in some newly recognized species, such as Akkermansia muciniphila, Segmented filamentous bacteria and Faecalibacterium prausnitzii, which seem to have an impact on more or less severe disease in specific models. Thus, the impact of the microbiota on animal models is of a magnitude that cannot be ignored in future research. Therefore, either models with specific microbiota must be developed, or the microbiota must be characterized in individual studies and incorporated into data evaluation.

Full Text Available Background. Recently, the importance of the gutmicrobiota in the pathogenesis of several disorders has gained clinical interests. Among exogenous factors affecting gut microbiome, diet appears to have the largest effect. Fatty acids, especially omega-3 polyunsaturated, ameliorate a range of several diseases, including cardiometabolic and inflammatory and cancer. Fatty acids associated beneficial effects may be mediated, to an important extent, through changes in gutmicrobiota composition. We sought to understand the changes of the gutmicrobiota in response to an omega-3 rich diet. Case Presentation. This case study investigated changes of gutmicrobiota with an omega-3 rich diet. Fecal samples were collected from a 45-year-old male who consumed 600 mg of omega-3 daily for 14 days. After the intervention, species diversity was decreased, but several butyrate-producing bacteria increased. There was an important decrease in Faecalibacterium prausnitzii and Akkermansia spp. Gutmicrobiota changes were reverted after the 14-day washout. Conclusion. Some of the health-related benefits of omega-3 may be due, in part, to increases in butyrate-producing bacteria. These findings may shed light on the mechanisms explaining the effects of omega-3 in several chronic diseases and may also serve as an existing foundation for tailoring personalized medical treatments.

Full Text Available This review examines whether there is evidence that a strict vegan diet confers health advantages beyond that of a vegetarian diet or overall healthy eating. Few studies include vegan subjects as a distinct experimental group, yet when vegan diets are directly compared to vegetarian and omnivorous diets, a pattern of protective health benefits emerges. The relatively recent inclusion of vegan diets in studies of gutmicrobiota and health allows us the opportunity to assess whether the vegan gutmicrobiota is distinct, and whether the health advantages characteristic of a vegan diet may be partially explained by the associated microbiota profile. The relationship between diet and the intestinal microbial profile appears to follow a continuum, with vegans displaying a gutmicrobiota most distinct from that of omnivores, but not always significantly different from that of vegetarians. The vegan gut profile appears to be unique in several characteristics, including a reduced abundance of pathobionts and a greater abundance of protective species. Reduced levels of inflammation may be the key feature linking the vegan gutmicrobiota with protective health effects. However, it is still unclear whether a therapeutic vegan diet can be prescribed to alter the gut microflora for long-term health benefits.

This review examines whether there is evidence that a strict vegan diet confers health advantages beyond that of a vegetarian diet or overall healthy eating. Few studies include vegan subjects as a distinct experimental group, yet when vegan diets are directly compared to vegetarian and omnivorous diets, a pattern of protective health benefits emerges. The relatively recent inclusion of vegan diets in studies of gutmicrobiota and health allows us the opportunity to assess whether the vegan gutmicrobiota is distinct, and whether the health advantages characteristic of a vegan diet may be partially explained by the associated microbiota profile. The relationship between diet and the intestinal microbial profile appears to follow a continuum, with vegans displaying a gutmicrobiota most distinct from that of omnivores, but not always significantly different from that of vegetarians. The vegan gut profile appears to be unique in several characteristics, including a reduced abundance of pathobionts and a greater abundance of protective species. Reduced levels of inflammation may be the key feature linking the vegan gutmicrobiota with protective health effects. However, it is still unclear whether a therapeutic vegan diet can be prescribed to alter the gut microflora for long-term health benefits.

The gutmicrobiota of insects contributes positively to the physiology of its host mainly by participating in food digestion, protecting against pathogens, or provisioning vitamins or amino acids, but the dynamics of this complex ecosystem is not well understood so far. In this study, we have characterized the gutmicrobiota of the omnivorous cockroach Blattella germanica by pyrosequencing the hypervariable regions V1-V3 of the 16S rRNA gene of the whole bacterial community. Three diets differing in the protein content (0, 24 and 50%) were tested at two time points in lab-reared individuals. In addition, the gutmicrobiota of wild adult cockroaches was also analyzed. In contrast to the high microbial richness described on the studied samples, only few species are shared by wild and lab-reared cockroaches, constituting the bacterial core in the gut of B. germanica. Overall, we found that the gutmicrobiota of B. germanica is highly dynamic as the bacterial composition was reassembled in a diet-specific manner over a short time span, with no-protein diet promoting high diversity, although the highest diversity was found in the wild cockroaches analyzed. We discuss how the flexibility of the gutmicrobiota is probably due to its omnivorous life style and varied diets.

Full Text Available It is acknowledged that some obesity trajectories are set early in life, and that rapid weight gain in infancy is a risk factor for later development of obesity. Identifying modifiable factors associated with early rapid weight gain is a prerequisite for curtailing the growing worldwide obesity epidemic. Recently, much attention has been given to findings indicating that gutmicrobiota may play a role in obesity development. We aim at identifying how the development of early gutmicrobiota is associated with expected infant growth. We developed a novel procedure that allows for the identification of longitudinal gutmicrobiota patterns (corresponding to the gut ecosystem developing, which are associated with an outcome of interest, while appropriately controlling for the false discovery rate. Our method identified developmental pathways of Staphylococcus species and Escherichia coli that were associated with expected growth, and traditional methods indicated that the detection of Bacteroides species at day 30 was associated with growth. Our method should have wide future applicability for studying gutmicrobiota, and is particularly important for translational considerations, as it is critical to understand the timing of microbiome transitions prior to attempting to manipulate gutmicrobiota in early life.

Antimicrobials have been used in swine production at subtherapeutic levels since the early 1950s to increase feed efficiency and promote growth. In North America, a number of antimicrobials are available for use in swine. However, the continuous administration of subtherapeutic, low concentrations of antimicrobials to pigs also provides selective pressure for antimicrobial-resistant bacteria and resistance determinants. For this reason, subtherapeutic antimicrobial use in livestock remains a source of controversy and concern. The swine gutmicrobiota demonstrates a number of changes in response to antimicrobial administration depending on the dosage, duration of treatment, age of the pigs, and gut location that is sampled. Both culture-independent and -dependent studies have also shown that the swine gutmicrobiota contains a large number of antimicrobial resistance determinants even in the absence of antimicrobial exposure. Heavy metals, such as zinc and copper, which are often added at relatively high doses to swine feed, may also play a role in maintaining antimicrobial resistance and in the stability of the swine gutmicrobiota. This review focuses on the use of antimicrobials in swine production, with an emphasis on the North American regulatory context, and their effect on the swine gutmicrobiota and on antimicrobial resistance determinants in the gutmicrobiota.

Lotus seed resistant starch, known as resistant starch type 3 (LRS3), was orally administered to mice to investigate its effects on the gutmicrobiota, short-chain fatty acids (SCFAs) production, and mineral absorption. The results showed that mice fed LRS3 displayed a lower level of gut bacterial diversity than other groups. The numbers of starch-utilizing and butyrate-producing bacteria, such as Lactobacillus and Bifidobacterium, and Lachnospiraceae, Ruminococcaceae, and Clostridium, respectively, in mice increased after the administration of medium and high doses of LRS3, while those of Rikenellaceae and Porphyromonadaceae decreased. Furthermore, SCFAs and lactic acid in mice feces were affected by LRS3, and lactate was fermented to butyrate by gutmicrobiota. LRS3 enhanced the intestinal absorption of calcium, magnesium, and iron, and this was dependent on the type and concentration of SCFAs, especially butyrate. Thus, LRS3 promoted the production of SCFAs and mineral absorption by regulating gutmicrobiota in mice.

The human gutmicrobiota is linked to a variety of human health issues and implicated in antibiotic resistance gene dissemination. Most of these associations rely on culture-independent methods, since it is commonly believed that gutmicrobiota cannot be easily or sufficiently cultured. Here, we...... show that carefully designed conditions enable cultivation of a representative proportion of human gut bacteria, enabling rapid multiplex phenotypic profiling. We use this approach to determine the phylogenetic distribution of antibiotic tolerance phenotypes for 16 antibiotics in the human gut...... microbiota. Based on the phenotypic mapping, we tailor antibiotic combinations to specifically select for previously uncultivated bacteria. Utilizing this method we cultivate and sequence the genomes of four isolates, one of which apparently belongs to the genus Oscillibacter; uncultivated Oscillibacter...

Full Text Available Clostridium difficile infection (CDI is the most important cause of nosocomial diarrhea. Broad-spectrum antimicrobials have profound detrimental effects on the structure and diversity of the indigenous intestinal microbiota. These alterations often impair colonization resistance, allowing the establishment and proliferation of C. difficile in the gut. Studies involving animal models have begun to decipher the precise mechanisms by which the intestinal microbiota mediates colonization resistance against C. difficile and numerous investigations have described gutmicrobiota alterations associated with C. difficile colonization or infection in human subjects. Fecal microbiota transplantation (FMT is a highly effective approach for the treatment of recurrent CDI that allows the restoration of a healthy intestinal ecosystem via infusion of fecal material from a healthy donor. The recovery of the intestinal microbiota after FMT has been examined in a few reports and work is being done to develop custom bacterial community preparations that could be used as a replacement for fecal material.

Iron (Fe) has been widely applied to treat arsenic (As)-contaminated water, and Fe could influence bioavailability and toxicity of As. However, little is known about the impact of As and/or Fe on gutmicrobiota, which plays important roles in host health. In this study, high-throughput sequencing and quantitative real time PCR were applied to analyze the impact of As and Fe on mouse gutmicrobiota. Co-exposure of As and Fe mitigated effects on microbial community to a certain extent. Correlation analysis showed the shifts in gutmicrobiota caused by As and/or Fe exposure might be important reason of changes in metabolic profiles of mouse. For antibiotic resistance genes (ARGs), co-exposure of As and Fe increased types and abundance of ARGs. But for high abundance ARGs, such as tetQ, tetO and tetM, co-exposure of As and Fe mitigated effects on their abundances compared to exposure to As and Fe alone. No obvious relationship between ARGs and mobile genetic elements were found. The changes in ARGs caused by metal exposure might be due to the alteration of gut microbial diversity. Our results show that changes of gut microbial community caused by As and/or Fe can influence host metabolisms and abundances of ARGs in gut, indicating that changes of gutmicrobiota should be considered during the risk assessment of As and/or Fe.

Full Text Available Abstract Background A modest number of prospective studies of the composition of the intestinal microbiota and eczema in early life have yielded conflicting results. Objective To examine the relationship between the bacterial diversity of the gut and the development of eczema in early life by methods other than stool culture. Methods Fecal samples were collected from 21 infants at 1 and 4 months of life. Nine infants were diagnosed with eczema by the age of 6 months (cases and 12 infants were not (controls. After conducting denaturating gradient gel electrophoresis (DGGE of stool samples, we compared the microbial diversity of cases and controls using the number of electrophoretic bands and the Shannon index of diversity (H' as indicators. Results Control subjects had significantly greater fecal microbial diversity than children with eczema at ages 1 (mean H' for controls = 0.75 vs. 0.53 for cases, P = 0.01 and 4 months (mean H' for controls = 0.92 vs. 0.59 for cases, P = 0.02. The increase in diversity from 1 to 4 months of age was significant in controls (P = 0.04 but not in children who developed eczema by 6 months of age (P = 0.32. Conclusion Our findings suggest that reduced microbial diversity is associated with the development of eczema in early life.

The microbiota of the gut has many crucial functions in human health. Dysbiosis of the microbiota has been correlated to a large and still increasing number of diseases. Recent studies have mostly focused on analyzing the associations between disease and an aberrant microbiota composition. Functiona

Increasing evidence of tight links among the gutmicrobiota, obesity, and host health has emerged, but knowledge of the ecological processes that shape the variation in microbial assemblages across growth rates remains elusive. Moreover, inadequately control for differences in factors that profoundly affect the gut microbial community, hampers evaluation of the gutmicrobiota roles in regulating growth rates. To address this gap, we evaluated the composition and ecological processes of the gut bacterial community in cohabitating retarded, overgrown, and normal shrimps from identically managed ponds. Gut bacterial community structures were distinct (P = 0.0006) among the shrimp categories. Using a structural equation modeling (SEM), we found that changes in the gut bacterial community were positively related to digestive activities, which subsequently affected shrimp growth rate. This association was further supported by intensified interspecies interaction and enriched lineages with high nutrient intake efficiencies in overgrown shrimps. However, the less phylogenetic clustering of gutmicrobiota in overgrown and retarded subjects may offer empty niches for pathogens invasion, as evidenced by higher abundances of predicted functional pathways involved in disease infection. Given no differences in biotic and abiotic factors among the cohabitating shrimps, we speculated that the distinct gut community assembly could be attributed to random colonization in larval shrimp (e.g., priority effects) and that an altered microbiota could be a causative factor in overgrowth or retardation in shrimp. To our knowledge, this is the first study to provide an integrated overview of the direct roles of gutmicrobiota in shaping shrimp growth rate and the underlying ecological mechanisms.

Full Text Available Abstract Obesity is a chronic disease characterized by persistent low-grade inflammation with alterations in gut motility. Motor abnormalities suggest that obesity has effects on the enteric nervous system (ENS, which controls virtually all gut functions. Recent studies have revealed that the gutmicrobiota can affect obesity and increase inflammatory tone by modulating mucosal barrier function. Furthermore, the observation that inflammatory conditions influence the excitability of enteric neurons may add to the gut dysfunction in obesity. In this article, we discuss recent advances in understanding the role of gutmicrobiota and inflammation in the pathogenesis of obesity and obesity-related gastrointestinal dysfunction. The potential contribution of sirtuins in protecting or regulating the circuitry of the ENS under inflamed states is also considered.

There is growing recognition that composition and metabolic activity of the gutmicrobiota can be modulated by the dietary proteins which in turn impact health. The amino acid composition and digestibility of proteins, which are influenced by its source and amount of intake, play a pivotal role in determining the microbiota. Reciprocally, it appears that the gutmicrobiota is also able to affect protein metabolism which give rise to the view that function between the microbiota and protein can proceed in both directions. In response to the alterations in dietary protein components, there are significant changes in the microbial metabolites including short chain fatty acids (SCFAs), ammonia, amines, gases such as hydrogen, sulfide and methane which are cytotoxins, genotoxins and carcinogens associated with development of colon cancer and inflammatory bowel diseases. A suitable ratio between protein and carbohydrate or even a low protein diet is recommended based on the evidence that excessive protein intake adversely affect health. Supplying high and undigested proteins will encourage pathogens and protein-fermenting bacteria to increase the risk of diseases. These changes of microbiota can affect gut barrier and immune system by regulating genes expression in relevant signaling pathways and by regulating the secretion of metabolites. The objective of this review is to assess the impact of dietary proteins on microbiota composition and activity in the gastro-intestinal tract. The attention should be give to the dietary strategies with judicious selection of source and supplementation of dietary protein to benefit gut health.

The use of antibiotics in swine production for the purpose of growth promotion dates back to the 1950s. Despite this long history of use, the exact mechanism(s) responsible for the growth-promoting effects of antibiotics in swine remain largely unknown. It is believed, however, that growth promotion is due to antibiotics having a direct impact on the gutmicrobiota. In this study, the effect of two antibiotics on the swine gutmicrobiota over a 19-week monitoring period was investigated using Illumina-based sequencing. A shift in the relative abundance of several taxa and in 26 operational taxonomic units (OTUs) was observed in pigs fed subtherapeutic concentrations of tylosin (44-11 mg kg(-1) feed). Only minor alterations were noted with the administration of chlortetracycline at 5.5 mg kg(-1) feed. The most notable changes in the relative abundance of taxa and OTUs were noted between suckling piglets and postweaned pigs. Diversity was also reduced in the gutmicrobiota of suckling piglets as measured using the Shannon, Chao1, and phylogenetic diversity indices. These results show that the effect of antibiotics on the swine gutmicrobiota is variable based on dosage and duration and that the swine gutmicrobiota exhibits considerable resilience to long-term changes due to antibiotic perturbations.

Clostridium difficile is well recognized as the common pathogen of nosocomial diarrhea, meanwhile, asymptomatic colonization with C. difficile in part of the population has also drawn public attention. Although gutmicrobiota is known to play an important role in the pathogenesis of C. difficile infection (CDI), whether there is any alteration of gut microbial composition in asymptomatic C. difficile carriers hasn't been clearly described. The purpose of this study was to explore the differences in gut microbiome among CDI patients, asymptomatic C. difficile carriers and healthy individuals. We performed fecal microbiota analysis on the samples of eight CDI patients, eight asymptomatic C. difficile carriers and nine healthy subjects using 16S rRNA gene pyrosequencing. CDI patients and asymptomatic carriers showed reduced microbial richness and diversity compared with healthy subjects, accompanied with a paucity of phylum Bacteroidetes and Firmicutes as well as an overabundance of Proteobacteria. Some normally commensal bacteria, especially butyrate producers, were significantly depleted in CDI patients and asymptomatic carriers. Furthermore, the differences observed in microbial community structure between CDI patients and asymptomatic carriers suggested that the gutmicrobiota may be a potential factor of disease state for CDI. Our study demonstrates the characterization and diversity of gutmicrobiota in CDI and asymptomatic C. difficile colonization, which will provide new ideas for surveillance of the disease state and development of microbiota-targeted agents for CDI prevention and treatment.

Nonalcoholic fatty liver disease (NAFLD) is a major clinical consequence for people with obesity and metabolic syndrome and is also associated with enteral and parenteral nutrition. Early studies suggested that altered gutmicrobiota might contribute to obesity by affecting energy harvest from the diet and energy storage in the host. Recent evidence in humans as well as in animal models has linked gutmicrobiota to the development of NAFLD through the gut-liver axis. With bacterial overgrowth and increased intestinal permeability observed in patients with NAFLD and in animal models, gut-derived bacterial products such as endotoxin (lipopolysaccharide) and bacterial DNA are being delivered to the liver through the portal vein and then activate Toll-like receptors (TLRs), mainly TLR4 and TLR9, and their downstream cytokines and chemokines, leading to the development and progression of NAFLD. Given the limited data in humans, the role of gutmicrobiota in the pathogenesis of NAFLD is still open to discussion. Prebiotics and probiotics have been attempted to modify the microbiota as preventive or therapeutic strategies on this pathological condition. Their beneficial effects on NALFD have been demonstrated in animal models and limited human studies. However, prospective, appropriately powered, randomized, controlled clinical trials are needed to determine whether prebiotics and probiotics and other integrated strategies to modify intestinal microbiota are efficacious therapeutic modalities to treat NALFD.

Cystic fibrosis (CF) is characterised by many comorbidities related to aberrant mucosa and chronic inflammation in the respiratory and digestive systems. The intestinal mucosa serves as the primary interface between the gutmicrobiota and endocrine, neural and immune systems. There is emerging evidence that aberrant intestinal mucosa in CF may associate with an altered gutmicrobiota. Compared to healthy subjects, the overall bacterial abundance and species richness seems to be reduced in CF, accompanied by a trend in suppression of Firmicutes and Bacteroidetes spp. and an augmentation of potentially pathogenic species. There is also some concordance of gut and respiratory microbiotas in CF infants over time. The clinical significance of these observations awaits investigation. The gutmicrobiota have some potential in CF management by affecting inflammatory and immune responses, and influencing aberrant mucosa. As an important modifiable factor, diet therapies such as probiotics and prebiotics have shown initial promise in improving CF related conditions associated with chronic inflammation. More studies are needed to confirm this, as well as the efficacy of other dietary strategies such as modulating dietary fat and indigestible carbohydrate. Similarly, dietary modification of gutmicrobiota to optimise nutritional status in CF may be feasible, although more CF-specific studies are warranted.

Perturbations of the composition and function of the gutmicrobiota have been associated with metabolic disorders including obesity, insulin resistance and type 2 diabetes. Studies on mice have demonstrated several underlying mechanisms including host signalling through bacterial lipopolysaccharides derived from the outer membranes of Gram-negative bacteria, bacterial fermentation of dietary fibres to short-chain fatty acids and bacterial modulation of bile acids. On top of this, an increased permeability of the intestinal epithelium may lead to increased absorption of macromolecules from the intestinal content resulting in systemic immune responses, low-grade inflammation and altered signalling pathways influencing lipid and glucose metabolism. While mechanistic studies on mice collectively support a causal role of the gutmicrobiota in metabolic diseases, the majority of studies in humans are correlative of nature and thus hinder causal inferences. Importantly, several factors known to influence the risk of type 2 diabetes, e.g. diet and age, have also been linked to alterations in the gutmicrobiota complicating the interpretation of correlative studies. However, based upon the available evidence, it is hypothesised that the gutmicrobiota may mediate or modulate the influence of lifestyle factors triggering development of type 2 diabetes. Thus, the aim of this review is to critically discuss the potential role of the gutmicrobiota in the pathophysiology and pathogenesis of type 2 diabetes.

Each individual can be distinguished by the heterogeneity of the trillions of microbes inhabiting his gastrointestinal tract. This concept, together with the role that gutmicrobiota is considered to play in the induction of metabolic diseases, paves the way for the development of personalized medicine. By exploiting our unique animal model of metabolic adaptation to a high-fat diet, we have recently shown that differential gutmicrobiota lead to different metabolic phenotypes--metabotypes. Moreover, we have also reported that a given metabotype can be distinguished by different profiles of gut microbes, symptomatic of the complexity of the regulation of host physiology by gutmicrobiota. Furthermore, in an effort to find bacterial predictors of type 2 diabetes (T2D), we discovered that in a healthy population, subjects who subsequently developed T2D had increased blood levels of bacterial 16S rDNA well before. In addition, tissue (blood) microbiota, mainly characterized by Proteobacteria (up to 90%), has been discovered both in healthy individuals and in diabetic patients. Altogether, our results confirm the presence of gut microbes and propose tissue microbiota as new targets for the innovative treatment of T2D.

Gutmicrobiota, its evolutive dynamics and influence on host through its protective, trophic and metabolic actions, has a key role in health and opens unique opportunities for the identification of new markers of the physiopathological state of each individual. Alterations in gutmicrobiota composition have been associated with plenty disorders. Of interest, the vast number of studies demonstrates the role of microbiota in obesity, a serious public health problem that has reached epidemic proportions in many developed and middle-income countries. The economic and health costs of this condition and its comorbidities such as fatty liver, insulin resistance/diabetes, or cardiovascular events are considerable. Therefore, every strategy designed to reduce obesity would imply important savings. Targeting microbiota, in order to restore/modulate the microbiota composition with antibiotics, probiotics, prebiotics, or even fecal transplants, is considered as a promising strategy for the development of new solutions for the treatment of obesity. However, there is still lot to do in this field in order to identify the exact composition of microbiota in "health" and the specific mechanisms that regulate the host-microbiotal crosstalk. In addition, it is important to note that changes not only in the gutmicrobiota profile (abundance) but also in its metabolism and functions need to be taken into account in the context of contribution in the physiopathology of obesity and related disorders.

Full Text Available The composition of the gutmicrobiota of mammals is greatly influenced by diet. Therefore, evaluation of different food ingredients that may promote changes in the gutmicrobiota composition is an attractive approach to treat microbiota disturbances. In this study, three dietary fibers, such as inulin (I, 10%, resistant starch (RS, 10%, and citrus pectin (3%, were employed as supplements to normal chow diet of adult male rats for 2 weeks. Fecal microbiota composition and corresponding metabolite profiles were assessed before and after prebiotics supplementation. A general increase in the Bacteroidetes phylum was detected with a concurrent reduction in Firmicutes, in particular for I and RS experiments, while additional changes in the microbiota composition were evident at lower taxonomic levels for all the three substrates. Such modifications in the microbiota composition were correlated with changes in metabolic profiles of animals, in particular changes in acetate and succinate levels. This study represents a first attempt to modulate selectively the abundance and/or metabolic activity of various members of the gutmicrobiota by means of dietary fiber.

Full Text Available The commensal microbiota is in constant interaction with the immune system, teaching immune cells to respond to antigens. Studies in mice have demonstrated that manipulation of the intestinal microbiota alters host immune cell homeostasis. Additionally, metagenomic-sequencing analysis has revealed alterations in intestinal microbiota in patients suffering from inflammatory bowel disease, asthma, and obesity. Perturbations in the microbiota composition result in a deficient immune response and impaired tolerance to commensal microorganisms. Due to altered microbiota composition which is associated to some inflammatory diseases, several strategies, such as the administration of probiotics, diet, and antibiotic usage, have been utilized to prevent or ameliorate chronic inflammatory diseases. The purpose of this review is to present and discuss recent evidence showing that the gutmicrobiota controls immune system function and onset, development, and resolution of some common inflammatory diseases.

The gutmicrobiota, which is considered a causal factor in metabolic diseases as shown best in animals, is under the dual influence of the host genome and nutritional environment. This study investigated whether the gutmicrobiota per se, aside from changes in genetic background and diet, could sign different metabolic phenotypes in mice. The unique animal model of metabolic adaptation was used, whereby C57Bl/6 male mice fed a high-fat carbohydrate-free diet (HFD) became either diabetic (HFD diabetic, HFD-D) or resisted diabetes (HFD diabetes-resistant, HFD-DR). Pyrosequencing of the gutmicrobiota was carried out to profile the gut microbial community of different metabolic phenotypes. Inflammation, gut permeability, features of white adipose tissue, liver and skeletal muscle were studied. Furthermore, to modify the gutmicrobiota directly, an additional group of mice was given a gluco-oligosaccharide (GOS)-supplemented HFD (HFD+GOS). Despite the mice having the same genetic background and nutritional status, a gut microbial profile specific to each metabolic phenotype was identified. The HFD-D gut microbial profile was associated with increased gut permeability linked to increased endotoxaemia and to a dramatic increase in cell number in the stroma vascular fraction from visceral white adipose tissue. Most of the physiological characteristics of the HFD-fed mice were modulated when gutmicrobiota was intentionally modified by GOS dietary fibres. The gutmicrobiota is a signature of the metabolic phenotypes independent of differences in host genetic background and diet.

Chronic inflammation induced by endotoxin from a dysbiotic gutmicrobiota contributes to the development of obesity-related metabolic disorders. Modification of gutmicrobiota by a diet to balance its composition becomes a promising strategy to help manage obesity. A dietary scheme based on whole grains, traditional Chinese medicinal foods, and prebiotics (WTP diet) was designed to meet human nutritional needs as well as balance the gutmicrobiota. Ninety-three of 123 central obese volunteers (BMI ≥ 28 kg m(-2) ) completed a self-controlled clinical trial consisting of 9-week intervention on WTP diet followed by a 14-week maintenance period. The average weight loss reached 5.79 ± 4.64 kg (6.62 ± 4.94%), in addition to improvement in insulin sensitivity, lipid profiles, and blood pressure. Pyrosequencing of fecal samples showed that phylotypes related to endotoxin-producing opportunistic pathogens of Enterobacteriaceae and Desulfovibrionaceae were reduced significantly, while those related to gut barrier-protecting bacteria of Bifidobacteriaceae increased. Gut permeability, measured as lactulose/mannitol ratio, was decreased compared with the baseline. Plasma endotoxin load as lipopolysaccharide-binding protein was also significantly reduced, with concomitant decrease in tumor necrosis factor-α, interleukin-6, and an increase in adiponectin. These results suggest that modulation of the gutmicrobiota via dietary intervention may enhance the intestinal barrier integrity, reduce circulating antigen load, and ultimately ameliorate the inflammation and metabolic phenotypes.

vertically transmitted microbes or through the dietary habits of the family. Additionally, very little is known about the effect of diet during the complementary feeding period, which is potentially important for gutmicrobiota development. Here, the gutmicrobiotas of two different cohorts of infants, born...... either of a random sample of healthy mothers (n = 114), or of obese mothers (n = 113), were profiled by 16S rRNA amplicon sequencing. Gutmicrobiota data were compared to breastfeeding patterns and detailed individual dietary recordings to assess effects of the complementary diet. We found that maternal...... composition and alpha diversity were thus strongly affected by introduction of family foods with high protein and fiber contents. Specifically, intake of meats, cheeses and Danish rye bread, rich in protein and fiber, were associated with increased alpha diversity. Our results reveal that the transition from...

The human gut microbiome is composed of an enormous number of microorganisms, generally regarded as commensal bacteria. Without this inherent microbial community, we would be unable to digest plant polysaccharides and would have trouble extracting lipids from our diet. Resident gut bacteria are an important contributor to healthy metabolism and there is significant evidence linking gutmicrobiota and metabolic disorders such as obesity and diabetes. In the past few years, neuroscience research has demonstrated the importance of microbiota in the development of brain systems that are vital to both stress reactivity and stress-related behaviours. Here we review recent literature that examines the impact of diet-induced changes in the microbiota on stress-related behaviours including anxiety and depression.

The expansion of agriculture is shrinking pristine forest areas worldwide, jeopardizing the persistence of their wild inhabitants. The Udzungwa red colobus monkey (Procolobus gordonorum) is among the most threatened primate species in Africa. Primarily arboreal and highly sensitive to hunting and habitat destruction, they provide a critical model to understanding whether anthropogenic disturbance impacts gutmicrobiota diversity. We sampled seven social groups inhabiting two forests (disturbed vs. undisturbed) in the Udzungwa Mountains of Tanzania. While Ruminococcaceae and Lachnospiraceae dominated in all individuals, reflecting their role in extracting energy from folivorous diets, analysis of genus composition showed a marked diversification across habitats, with gutmicrobiota α-diversity significantly higher in the undisturbed forest. Functional analysis suggests that such variation may be associated with food plant diversity in natural versus human-modified habitats, requiring metabolic pathways to digest xenobiotics. Thus, the effects of changes in gutmicrobiota should not be ignored to conserve endangered populations.

The colonic microbiota undergoes certain age related changes that may affect health. For example, above the age of 55-65 y, populations of bifidobacteria are known to decrease markedly. Bifidobacteria are known inhibitors of pathogenic microbes and a decrease in their activities may increase susceptibility to infections. There is therefore interest in trying to reverse their decline in aged persons. As the gutmicrobiota responds to dietary intervention, both probiotics and prebiotics have been tested in this regard. Probiotics are live microbes in the diet, whereas prebiotics are fermentable ingredients that specifically target components of the indigenous microbiota seen to be beneficial. We have published a recent paper demonstrating that prebiotic galactooligosaccharides can exert power effects upon bifidobacteria in the gut flora of elderly persons (both in vivo and in vitro). This addendum summarizes research that led up to this study and discusses the possible impact of prebiotics in impacting upon the gut health of aged persons.

Full Text Available Multiple sclerosis (MS is an autoimmune neurological disease characterized by chronic inflammation of the central nervous system (CNS, leading to demyelination, axonal damage, and symptoms such as fatigue and disability. Although the cause of MS is not known, the infiltration of peripherally activated immune cells into the CNS has a key pathogenic role. Accumulating evidence supports an important role of diet and gutmicrobiota in immune-mediated diseases. Preclinical as well as clinical studies suggest a role for gutmicrobiota and dietary components in MS. Here, we review these recent studies on gutmicrobiota and dietary interventions in MS and its animal model experimental autoimmune encephalomyelitis. We also propose directions for future research.

Obesity and type 2 diabetes mellitus (T2DM) are attributed to a combination of genetic susceptibility and lifestyle factors. Their increasing prevalence necessitates further studies on modifiable causative factors and novel treatment options. The gutmicrobiota has emerged as an important contributor to the obesity--and T2DM--epidemic proposed to act by increasing energy harvest from the diet. Although obesity is associated with substantial changes in the composition and metabolic function of the gutmicrobiota, the pathophysiological processes remain only partly understood. In this review we will describe the development of the adult human microbiome and discuss how the composition of the gutmicrobiota changes in response to modulating factors. The influence of short-chain fatty acids, bile acids, prebiotics, probiotics, antibiotics and microbial transplantation is discussed from studies using animal and human models. Ultimately, we aim to translate these findings into therapeutic pathways for obesity and T2DM in humans.

The microbial community populating the human digestive tract has been linked to the development of obesity, diabetes and liver diseases. Proposed mechanisms on how the gutmicrobiota could contribute to obesity and metabolic diseases include: (1) improved energy extraction from diet by the conversion of dietary fibre to SCFA; (2) increased intestinal permeability for bacterial lipopolysaccharides (LPS) in response to the consumption of high-fat diets resulting in an elevated systemic LPS level and low-grade inflammation. Animal studies indicate differences in the physiologic effects of fermentable and non-fermentable dietary fibres as well as differences in long- and short-term effects of fermentable dietary fibre. The human intestinal microbiome is enriched in genes involved in the degradation of indigestible polysaccharides. The extent to which dietary fibres are fermented and in which molar ratio SCFA are formed depends on their physicochemical properties and on the individual microbiome. Acetate and propionate play an important role in lipid and glucose metabolism. Acetate serves as a substrate for de novo lipogenesis in liver, whereas propionate can be utilised for gluconeogenesis. The conversion of fermentable dietary fibre to SCFA provides additional energy to the host which could promote obesity. However, epidemiologic studies indicate that diets rich in fibre rather prevent than promote obesity development. This may be due to the fact that SCFA are also ligands of free fatty acid receptors (FFAR). Activation of FFAR leads to an increased expression and secretion of enteroendocrine hormones such as glucagon-like-peptide 1 or peptide YY which cause satiety. In conclusion, the role of SCFA in host energy balance needs to be re-evaluated.

Our gut harbors an extremely diverse collection of trillions of microbes that, besides degrading the complex dietary constituents, execute numerous activities vital for our metabolic and immune health. Although the importance of gutmicrobiota in maintaining digestive health has long been believed, its close correlation with numerous chronic ailments has recently been noticed, thanks to the innovative mechanistic studies on the compositional and functional aspects of gut microbial communities using germ-free or humanized animal models. Since a myriad of mysteries about the precise structures and functions of gut microbial communities in specific health situations still remains to be explicated, the emerging field of gutmicrobiota remains a foremost objective of research for microbiologists, immunologists, computational biologists, clinicians, food and nutrition experts, etc. Nevertheless, it is only after a comprehensive understanding of the structure, density, and function of the gutmicrobiota that the new therapeutic targets could be captured and utilized for a healthier gut as well as improved overall well-being.

The human gut harbors more than 100 trillion microbial cells, which have an essential role in human metabolic regulation via their symbiotic interactions with the host. Altered gut microbial ecosystems have been associated with increased metabolic and immune disorders in animals and humans. Molecular interactions linking the gutmicrobiota with host energy metabolism, lipid accumulation, and immunity have also been identified. However, the exact mechanisms that link specific variations in the composition of the gutmicrobiota with the development of obesity and metabolic diseases in humans remain obscure owing to the complex etiology of these pathologies. In this review, we discuss current knowledge about the mechanistic interactions between the gutmicrobiota, host energy metabolism, and the host immune system in the context of obesity and metabolic disease, with a focus on the importance of the axis that links gut microbes and host metabolic inflammation. Finally, we discuss therapeutic approaches aimed at reshaping the gut microbial ecosystem to regulate obesity and related pathologies, as well as the challenges that remain in this area.

Full Text Available Gutmicrobiota has shown tight and coordinated connection with various functions of its host such as metabolism, immunity, energy utilization, and health maintenance. To gain insight into whether gut microbes affect the metabolism of fish, we employed fast-growing transgenic common carp (Cyprinus carpio L. to study the connections between its large body feature and gut microbes. Metagenome-based fingerprinting and high-throughput sequencing on bacterial 16S rRNA genes indicated that fish gut was dominated by Proteobacteria, Fusobacteria, Bacteroidetes and Firmicutes, which displayed significant differences between transgenic fish and wild-type controls. Analyses to study the association of gut microbes with the fish metabolism discovered three major phyla having significant relationships with the host metabolic factors. Biochemical and histological analyses indicated transgenic fish had increased carbohydrate but decreased lipid metabolisms. Additionally, transgenic fish has a significantly lower Bacteroidetes:Firmicutes ratio than that of wild-type controls, which is similar to mammals between obese and lean individuals. These findings suggest that gutmicrobiotas are associated with the growth of fast growing transgenic fish, and the relative abundance of Firmicutes over Bacteroidetes could be one of the factors contributing to its fast growth. Since the large body size of transgenic fish displays a proportional body growth, which is unlike obesity in human, the results together with the findings from others also suggest that the link between obesity and gutmicrobiota is likely more complex than a simple Bacteroidetes:Firmicutes ratio change.

In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported. In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis. Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa. These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gutmicrobiota signatures of specific human diseases from those of medication.

Full Text Available BACKGROUND: The gut of most insects harbours nonpathogenic microorganisms. Recent work suggests that gutmicrobiota not only provide nutrients, but also involve in the development and maintenance of the host immune system. However, the complexity, dynamics and types of interactions between the insect hosts and their gutmicrobiota are far from being well understood. METHODS/PRINCIPAL FINDINGS: To determine the composition of the gutmicrobiota of two lepidopteran pests, Spodoptera littoralis and Helicoverpa armigera, we applied cultivation-independent techniques based on 16S rRNA gene sequencing and microarray. The two insect species were very similar regarding high abundant bacterial families. Different bacteria colonize different niches within the gut. A core community, consisting of Enterococci, Lactobacilli, Clostridia, etc. was revealed in the insect larvae. These bacteria are constantly present in the digestion tract at relatively high frequency despite that developmental stage and diet had a great impact on shaping the bacterial communities. Some low-abundant species might become dominant upon loading external disturbances; the core community, however, did not change significantly. Clearly the insect gut selects for particular bacterial phylotypes. CONCLUSIONS: Because of their importance as agricultural pests, phytophagous Lepidopterans are widely used as experimental models in ecological and physiological studies. Our results demonstrated that a core microbial community exists in the insect gut, which may contribute to the host physiology. Host physiology and food, nevertheless, significantly influence some fringe bacterial species in the gut. The gutmicrobiota might also serve as a reservoir of microorganisms for ever-changing environments. Understanding these interactions might pave the way for developing novel pest control strategies.

Full Text Available Characterization and understanding of gutmicrobiota has recently increased representing a wide research field, especially in autoimmune diseases. Gutmicrobiota is the major source of microbes which might exert beneficial as well as pathogenic effects on human health. Intestinal microbiome’s role as mediator of inflammation has only recently emerged. Microbiota has been observed to differ in subjects with early rheumatoid arthritis compared to controls, and this finding has commanded this study as a possible autoimmune process. Studies with intestinal microbiota have shown that rheumatoid arthritis is characterized by an expansion and/or decrease of bacterial groups as compared to controls. In this review, we present evidence linking intestinal dysbiosis with the autoimmune mechanisms involved in the development of rheumatoid arthritis.

Compartmentalization of the gastrointestinal (GI) tract of metazoans is critical for health. GI compartments contain specific microbiota, and microbiota dysbiosis is associated with intestinal dysfunction. Dysbiosis develops in aging intestines, yet how this relates to changes in GI compartmentalization remains unclear. The Drosophila GI tract is an accessible model to address this question. Here we show that the stomach-like copper cell region (CCR) in the middle midgut controls distribution and composition of the microbiota. We find that chronic activation of JAK/Stat signaling in the aging gut induces a metaplasia of the gastric epithelium, CCR decline, and subsequent commensal dysbiosis and epithelial dysplasia along the GI tract. Accordingly, inhibition of JAK/Stat signaling in the CCR specifically prevents age-related metaplasia, commensal dysbiosis and functional decline in old guts, and extends lifespan. Our results establish a mechanism by which age-related chronic inflammation causes the decline of intestinal compartmentalization and microbiota dysbiosis, limiting lifespan.

Probiotics are increasingly applied to prevent and treat a range of infectious, immune related and gastrointestinal diseases. Despite this, the mechanisms behind the putative effects of probiotics are poorly understood. One of the suggested modes of probiotic action is modulation of the endogenous...... gutmicrobiota, however probiotic intervention studies in adults have failed to show significant effects on gutmicrobiota composition. The gutmicrobiota of young children is known to be unstable and more responsive to external factors than that of adults. Therefore, potential effects of probiotic...... intervention on gutmicrobiota may be easier detectable in early life. We thus investigated the effects of a 6 month placebo-controlled probiotic intervention with Bifidobacterium animalis subsp. lactis (BB-12®) and Lactobacillus rhamnosus (LGG®) on gutmicrobiota composition and diversity in more than 200...

OBJECTIVE: Magnesium deficiency has been associated with anxiety in humans, and rodent studies have demonstrated the gutmicrobiota to impact behaviour. METHODS: We investigated the impact of 6 weeks of dietary magnesium deficiency on gutmicrobiota composition and anxiety-like behaviour...... and whether there was a link between the two. A total of 20 C57BL/6 mice, fed either a standard diet or a magnesium-deficient diet for 6 weeks, were tested using the light-dark box anxiety test. Gutmicrobiota composition was analysed by denaturation gradient gel electrophoresis. RESULTS: We demonstrated...... that the gutmicrobiota composition correlated significantly with the behaviour of dietary unchallenged mice. A magnesium-deficient diet altered the gutmicrobiota, and was associated with altered anxiety-like behaviour, measured by decreased latency to enter the light box. CONCLUSION: Magnesium deficiency...

Magnesium deficiency has been associated with anxiety in humans, and rodent studies have demonstrated the gutmicrobiota to impact behaviour. We investigated the impact of 6 weeks of dietary magnesium deficiency on gutmicrobiota composition and anxiety-like behaviour and whether there was a link between the two. A total of 20 C57BL/6 mice, fed either a standard diet or a magnesium-deficient diet for 6 weeks, were tested using the light-dark box anxiety test. Gutmicrobiota composition was analysed by denaturation gradient gel electrophoresis. We demonstrated that the gutmicrobiota composition correlated significantly with the behaviour of dietary unchallenged mice. A magnesium-deficient diet altered the gutmicrobiota, and was associated with altered anxiety-like behaviour, measured by decreased latency to enter the light box. Magnesium deficiency altered behavior. The duration of magnesium deficiency is suggested to influence behaviour in the evaluated test.

Diabetes is a group of metabolic disorders characterized by persistent hyperglycemia and has become a major public health concern. Autoimmune type 1 diabetes (T1D) and insulin resistant type 2 diabetes (T2D) are the two main types. A combination of genetic and environmental factors contributes to the development of these diseases. Gutmicrobiota have emerged recently as an essential player in the development of T1D, T2D and obesity. Altered gutmicrobiota have been strongly linked to disease in both rodent models and humans. Both classic 16S rRNA sequencing and shot-gun metagenomic pyrosequencing analysis have been successfully applied to explore the gutmicrobiota composition and functionality. This review focuses on the association between gutmicrobiota and diabetes and discusses the potential mechanisms by which gutmicrobiota regulate disease development in T1D, T2D and obesity.

Different housing systems can be used in pig production and little is known about their effect on gutmicrobiota composition. In this study we characterized fecal microbiota by sequencing the rRNA genes in sows kept during gestation in conventional pens with a slatted floor and in